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Genomics of Rare Hematologic Cancers
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Genomics of Rare Hematologic Cancers

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 June 2022) | Viewed by 45577

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Francesc Solé

E-Mail Website
Guest Editor
1. MDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, 08916 Barcelona, Spain
2. Microarrays Unit, Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain
Interests: MDS; MDS/MPN; SNP arrays; cytogenetics; NGS; myeloid neoplasms

Special Issue Information

Dear Colleagues,

Leukemias and hematologic cancers occur with less frequency than solid tumors. The most frequent and well-known hematologic cancers could be summarized in chronic and acute myeloid and lymphoid leukemias, myelomas and lymphomas, as well as myelodysplastic syndromes and myeloproliferative neoplasms. In this Special Issue we selected some of the rarest types of hematologic cancers because there are few reviews about these diseases. Now, genomics defines the diagnosis, prognosis, and treatment of most cancers, and we want to present a review of how genomics is useful to define these rare diseases. In this Special Issue we will highlight the genomic information that will be very useful for clinicians to diagnose and treat these patients.

Dr. Francesc Solé
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Germline Gene Variants in Myeloid Neoplasms
  • chronic eosinophilic leukemia
  • GATA2
  • hairy cell leukemia
  • juvenile myelomonocytic leukemia
  • MALT
  • mastocytosis
  • plasma cell leukemia
  • splenic marginal cell lymphoma
  • T cell acute lymphoblastic leukemia

Published Papers (14 papers)

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Research

Jump to: Review

18 pages, 4478 KiB  
Article
TP53 Abnormalities Are Underlying the Poor Outcome Associated with Chromothripsis in Chronic Lymphocytic Leukemia Patients with Complex Karyotype
by Silvia Ramos-Campoy, Anna Puiggros, Joanna Kamaso, Sílvia Beà, Sandrine Bougeon, María José Larráyoz, Dolors Costa, Helen Parker, Gian Matteo Rigolin, María Laura Blanco, Rosa Collado, Idoya Ancín, Rocío Salgado, Marco A. Moro-García, Tycho Baumann, Eva Gimeno, Carol Moreno, Marta Salido, Xavier Calvo, María José Calasanz, Antonio Cuneo, Florence Nguyen-Khac, David Oscier, Claudia Haferlach, Jonathan C. Strefford, Jacqueline Schoumans and Blanca Espinetadd Show full author list remove Hide full author list
Cancers 2022, 14(15), 3715; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153715 - 29 Jul 2022
Cited by 6 | Viewed by 2354
Abstract
Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, [...] Read more.
Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes. Nine cth cases were analyzed using optical genome mapping (OGM). Patterns detected by genomic microarrays were compared and the prognostic value of cth was analyzed. Cth was distributed throughout the genome, with chromosomes 3, 6 and 13 being those most frequently affected. OGM detected 88.1% of the previously known copy number alterations and several additional cth-related rearrangements (median: 9, range: 3–26). Two patterns were identified: one with rearrangements clustered in the region with cth (3/9) and the other involving both chromothriptic and non-chromothriptic chromosomes (6/9). Cases with cth showed a shorter time to first treatment (TTFT) than non-cth patients (median TTFT: 2 m vs. 15 m; p = 0.013). However, when stratifying patients based on TP53 status, cth did not affect TTFT. Only TP53 maintained its significance in the multivariate analysis for TTFT, including cth and genome complexity defined by genomic microarrays (HR: 1.60; p = 0.029). Our findings suggest that TP53 abnormalities, rather than cth itself, underlie the poor prognosis observed in this subset. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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Review

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16 pages, 1197 KiB  
Review
The Clinical Spectrum, Diagnosis, and Management of GATA2 Deficiency
by Marta Santiago, Alessandro Liquori, Esperanza Such, Ángel Zúñiga and José Cervera
Cancers 2023, 15(5), 1590; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051590 - 03 Mar 2023
Cited by 5 | Viewed by 3032
Abstract
Hereditary myeloid malignancy syndromes (HMMSs) are rare but are becoming increasingly significant in clinical practice. One of the most well-known syndromes within this group is GATA2 deficiency. The GATA2 gene encodes a zinc finger transcription factor essential for normal hematopoiesis. Insufficient expression and [...] Read more.
Hereditary myeloid malignancy syndromes (HMMSs) are rare but are becoming increasingly significant in clinical practice. One of the most well-known syndromes within this group is GATA2 deficiency. The GATA2 gene encodes a zinc finger transcription factor essential for normal hematopoiesis. Insufficient expression and function of this gene as a result of germinal mutations underlie distinct clinical presentations, including childhood myelodysplastic syndrome and acute myeloid leukemia, in which the acquisition of additional molecular somatic abnormalities can lead to variable outcomes. The only curative treatment for this syndrome is allogeneic hematopoietic stem cell transplantation, which should be performed before irreversible organ damage happens. In this review, we will examine the structural characteristics of the GATA2 gene, its physiological and pathological functions, how GATA2 genetic mutations contribute to myeloid neoplasms, and other potential clinical manifestations. Finally, we will provide an overview of current therapeutic options, including recent transplantation strategies. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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16 pages, 300 KiB  
Review
Current Understanding of DDX41 Mutations in Myeloid Neoplasms
by Kunhwa Kim, Faustine Ong and Koji Sasaki
Cancers 2023, 15(2), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15020344 - 05 Jan 2023
Cited by 6 | Viewed by 3967
Abstract
The DEAD-box RNA helicase 41 gene, DDX41, is frequently mutated in hereditary myeloid neoplasms, identified in 2% of entire patients with AML/MDS. The pathogenesis of DDX41 mutation is related to the defect in the gene’s normal functions of RNA and innate immunity. [...] Read more.
The DEAD-box RNA helicase 41 gene, DDX41, is frequently mutated in hereditary myeloid neoplasms, identified in 2% of entire patients with AML/MDS. The pathogenesis of DDX41 mutation is related to the defect in the gene’s normal functions of RNA and innate immunity. About 80% of patients with germline DDX41 mutations have somatic mutations in another allele, resulting in the biallelic DDX41 mutation. Patients with the disease with DDX41 mutations reportedly often present with the higher-grade disease, but there are conflicting reports about its impact on survival outcomes. Recent studies using larger cohorts reported a favorable outcome with a better response to standard therapies in patients with DDX41 mutations to patients without DDX41 mutations. For stem-cell transplantation, it is important for patients with DDX41 germline mutations to identify family donors early to improve outcomes. Still, there is a gap in knowledge on whether germline DDX41 mutations and its pathology features can be targetable for treatment, and what constitutes an appropriate screening/surveillance strategy for identified carriers. This article reviews our current understanding of DDX41 mutations in myeloid neoplasms in pathologic and clinical features and their clinical implications. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
13 pages, 1394 KiB  
Review
Myelodysplastic Syndromes with Isolated del(5q): Value of Molecular Alterations for Diagnostic and Prognostic Assessment
by Pamela Acha, Mar Mallo and Francesc Solé
Cancers 2022, 14(22), 5531; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225531 - 10 Nov 2022
Cited by 1 | Viewed by 2024
Abstract
Myelodysplastic syndromes (MDS) are a group of clonal hematological neoplasms characterized by ineffective hematopoiesis in one or more bone marrow cell lineages. Consequently, patients present with variable degrees of cytopenia and dysplasia. These characteristics constitute the basis for the World Health Organization (WHO) [...] Read more.
Myelodysplastic syndromes (MDS) are a group of clonal hematological neoplasms characterized by ineffective hematopoiesis in one or more bone marrow cell lineages. Consequently, patients present with variable degrees of cytopenia and dysplasia. These characteristics constitute the basis for the World Health Organization (WHO) classification criteria of MDS, among other parameters, for the current prognostic scoring system. Although nearly half of newly diagnosed patients present a cytogenetic alteration, and almost 90% of them harbor at least one somatic mutation, MDS with isolated del(5q) constitutes the only subtype clearly defined by a cytogenetic alteration. The results of several clinical studies and the advances of new technologies have allowed a better understanding of the biological basis of this disease. Therefore, since the first report of the “5q- syndrome” in 1974, changes and refinements have been made in the definition and the characteristics of the patients with MDS and del(5q). Moreover, specific genetic alterations have been found to be associated with the prognosis and response to treatments. The aim of this review is to summarize the current knowledge of the molecular background of MDS with isolated del(5q), focusing on the clinical and prognostic relevance of cytogenetic alterations and somatic mutations. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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17 pages, 2968 KiB  
Review
Rosai–Dorfman Disease between Proliferation and Neoplasia
by Ismail Elbaz Younes, Lubomir Sokol and Ling Zhang
Cancers 2022, 14(21), 5271; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14215271 - 27 Oct 2022
Cited by 10 | Viewed by 3437
Abstract
Rosai–Dorfman disease (RDD) is a rare myeloproliferative disorder of histiocytes with a broad spectrum of clinical manifestations and peculiar morphologic features (accumulation of histiocytes with emperipolesis). Typically, the patient with RDD shows bilateral painless, massive cervical lymphadenopathy associated with B symptoms. Approximately 43% [...] Read more.
Rosai–Dorfman disease (RDD) is a rare myeloproliferative disorder of histiocytes with a broad spectrum of clinical manifestations and peculiar morphologic features (accumulation of histiocytes with emperipolesis). Typically, the patient with RDD shows bilateral painless, massive cervical lymphadenopathy associated with B symptoms. Approximately 43% of patients presented with extranodal involvement. According to the 2016 revised histiocytosis classification, RDD belongs to the R group, including familial and sporadic form (classical nodal, extranodal, unclassified, or RDD associated with neoplasia or immune disease). Sporadic RDD is often self-limited. Most RDD needs only local therapies. Nevertheless, a small subpopulation of patients may be refractory to conventional therapy and die of the disease. Recent studies consider RDD a clonal neoplastic process, as approximately 1/3 of these patients harbor gene mutations involving the MAPK/ERK pathway, e.g., NRAS, KRAS, MAP2K1, and, rarely, the BRAF mutation. In addition to typical histiocytic markers (S100/fascin/CD68/CD163, etc.), recent studies show that the histiocytes in RDD also express BCL-1 and OCT2, which might be important in pathogenesis. Additionally, the heterozygous germline mutation involving the FAS gene TNFRSF6 is identified in some RDD patients with an autoimmune lymphoproliferative syndrome type Ia. SLC29A3 germline mutation is associated with familial or Faisalabad histiocytosis and H syndrome. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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16 pages, 330 KiB  
Review
Genetics Abnormalities with Clinical Impact in Primary Cutaneous Lymphomas
by Fernando Gallardo and Ramon M. Pujol
Cancers 2022, 14(20), 4972; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14204972 - 11 Oct 2022
Cited by 5 | Viewed by 1962
Abstract
Primary cutaneous lymphomas comprise a heterogeneous group of extranodal non-Hodgkin lymphomas (NHL) that arise from skin resident lymphoid cells and are manifested by specific lymphomatous cutaneous lesions with no evidence of extracutaneous disease at the time of diagnosis. They may originate from mature [...] Read more.
Primary cutaneous lymphomas comprise a heterogeneous group of extranodal non-Hodgkin lymphomas (NHL) that arise from skin resident lymphoid cells and are manifested by specific lymphomatous cutaneous lesions with no evidence of extracutaneous disease at the time of diagnosis. They may originate from mature T-lymphocytes (70% of all cases), mature B-lymphocytes (25–30%) or, rarely, NK cells. Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of T-cell malignancies including Mycosis Fungoides (MF) the most frequent subtype, accounting for approximately half of CTCL, and Sézary syndrome (SS), which is an erythrodermic and leukemic subtype characterized by significant blood involvement. The mutational landscape of MF and SS by NGS include recurrent genomic alterations in the TCR signaling effectors (i.e., PLCG1), the NF-κB elements (i.e., CARD11), DNA damage/repair elements (TP53 or ATM), JAK/STAT pathway elements or epigenetic modifiers (DNMT3). Genomic copy number variations appeared to be more prevalent than somatic mutations. Other CTCL subtypes such as primary cutaneous anaplastic large cell lymphoma also harbor genetic alterations of the JAK/STAT pathway in up to 50% of cases. Recently, primary cutaneous aggressive epidermotropic T-cell lymphoma, a rare fatal subtype, was found to contain a specific profile of JAK2 rearrangements. Other aggressive cytotoxic CTCL (primary cutaneous γδ T-cell lymphomas) also show genetic alterations in the JAK/STAT pathway in a large proportion of patients. Thus, CTCL patients have a heterogeneous genetic/transcriptional and epigenetic background, and there is no uniform treatment for these patients. In this scenario, a pathway-based personalized management is required. Cutaneous B-cell lymphoma (CBCL) subtypes present a variable genetic profile. The genetic heterogeneity parallels the multiple types of specialized B-cells and their specific tissue distribution. Particularly, many recurrent hotspot and damaging mutations in primary cutaneous diffuse large B-cell lymphoma of the leg type, involving MYD88 gene, or BCL6 and MYC translocations and BLIMP1 or CDKN2A deletions are useful for diagnostic and prognostic purposes for this aggressive subtype from other indolent CBCL forms. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
18 pages, 2009 KiB  
Review
Beyond Pathogenic RUNX1 Germline Variants: The Spectrum of Somatic Alterations in RUNX1-Familial Platelet Disorder with Predisposition to Hematologic Malignancies
by Alisa Förster, Melanie Decker, Brigitte Schlegelberger and Tim Ripperger
Cancers 2022, 14(14), 3431; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143431 - 14 Jul 2022
Cited by 6 | Viewed by 2266
Abstract
Pathogenic loss-of-function RUNX1 germline variants cause autosomal dominantly-inherited familial platelet disorder with predisposition to hematologic malignancies (RUNX1-FPD). RUNX1-FPD is characterized by incomplete penetrance and a broad spectrum of clinical phenotypes, even within affected families. Heterozygous RUNX1 germline variants set the basis for leukemogenesis, [...] Read more.
Pathogenic loss-of-function RUNX1 germline variants cause autosomal dominantly-inherited familial platelet disorder with predisposition to hematologic malignancies (RUNX1-FPD). RUNX1-FPD is characterized by incomplete penetrance and a broad spectrum of clinical phenotypes, even within affected families. Heterozygous RUNX1 germline variants set the basis for leukemogenesis, but, on their own, they are not transformation-sufficient. Somatically acquired secondary events targeting RUNX1 and/or other hematologic malignancy-associated genes finally lead to MDS, AML, and rarely other hematologic malignancies including lymphoid diseases. The acquisition of different somatic variants is a possible explanation for the variable penetrance and clinical heterogeneity seen in RUNX1-FPD. However, individual effects of secondary variants are not yet fully understood. Here, we review 91 cases of RUNX1-FPD patients who predominantly harbor somatic variants in genes such as RUNX1, TET2, ASXL1, BCOR, PHF6, SRSF2, NRAS, and DNMT3A. These cases illustrate the importance of secondary events in the development and progression of RUNX1-FPD-associated hematologic malignancies. The leukemia-driving interplay of predisposing germline variants and acquired variants remain to be elucidated to better understand clonal evolution and malignant transformation and finally allow risk-adapted surveillance and targeted therapeutic measures to prevent leukemia. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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25 pages, 1485 KiB  
Review
Comprehensive Analysis of Acquired Genetic Variants and Their Prognostic Impact in Systemic Mastocytosis
by Oscar González-López, Javier I. Muñoz-González, Alberto Orfao, Iván Álvarez-Twose and Andrés C. García-Montero
Cancers 2022, 14(10), 2487; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14102487 - 18 May 2022
Cited by 5 | Viewed by 3045
Abstract
Systemic mastocytosis (SM) is a rare clonal haematopoietic stem cell disease in which activating KIT mutations (most commonly KIT D816V) are present in virtually every (>90%) adult patient at similar frequencies among non-advanced and advanced forms of SM. The KIT D816V mutation is [...] Read more.
Systemic mastocytosis (SM) is a rare clonal haematopoietic stem cell disease in which activating KIT mutations (most commonly KIT D816V) are present in virtually every (>90%) adult patient at similar frequencies among non-advanced and advanced forms of SM. The KIT D816V mutation is considered the most common pathogenic driver of SM. Acquisition of this mutation early during haematopoiesis may cause multilineage involvement of haematopoiesis by KIT D816V, which has been associated with higher tumour burden and additional mutations in other genes, leading to an increased rate of transformation to advanced SM. Thus, among other mutations, alterations in around 30 genes that are also frequently mutated in other myeloid neoplasms have been reported in SM cases. From these genes, 12 (i.e., ASXL1, CBL, DNMT3A, EZH2, JAK2, KRAS, NRAS, SF3B1, RUNX1, SF3B1, SRSF2, TET2) have been recurrently reported to be mutated in SM. Because of all the above, assessment of multilineage involvement of haematopoiesis by the KIT D816V mutation, in the setting of multi-mutated haematopoiesis as revealed by a limited panel of genes (i.e., ASXL1, CBL, DNMT3A, EZH2, NRAS, RUNX1 and SRSF2) and associated with a poorer patient outcome, has become of great help to identify SM patients at higher risk of disease progression and/or poor survival who could benefit from closer follow-up and eventually also early cytoreductive treatment. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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19 pages, 1150 KiB  
Review
Latest Contributions of Genomics to T-Cell Acute Lymphoblastic Leukemia (T-ALL)
by Eulàlia Genescà and Celia González-Gil
Cancers 2022, 14(10), 2474; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14102474 - 17 May 2022
Cited by 2 | Viewed by 2740
Abstract
As for many neoplasms, initial genetic data about T-cell acute lymphoblastic leukemia (T-ALL) came from the application of cytogenetics. This information helped identify some recurrent chromosomal alterations in T-ALL at the time of diagnosis, although it was difficult to determine their prognostic impact [...] Read more.
As for many neoplasms, initial genetic data about T-cell acute lymphoblastic leukemia (T-ALL) came from the application of cytogenetics. This information helped identify some recurrent chromosomal alterations in T-ALL at the time of diagnosis, although it was difficult to determine their prognostic impact because of their low incidence in the specific T-ALL cohort analyzed. Genetic knowledge accumulated rapidly following the application of genomic techniques, drawing attention to the importance of using high-resolution genetic techniques to detect cryptic aberrations present in T-ALL, which are not usually detected by cytogenetics. We now have a clearer appreciation of the genetic landscape of the different T-ALL subtypes at diagnosis, explaining the particular oncogenetic processes taking place in each T-ALL, and we have begun to understand relapse-specific mechanisms. This review aims to summarize the latest advances in our knowledge of the genome in T-ALL. We highlight areas where the research in this subtype of ALL is progressing with the aim of identifying key questions that need to be answered in the medium-long term if this knowledge is to be applied in clinics. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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13 pages, 679 KiB  
Review
Genomics of Plasma Cell Leukemia
by Elizabeta A. Rojas and Norma C. Gutiérrez
Cancers 2022, 14(6), 1594; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14061594 - 21 Mar 2022
Cited by 5 | Viewed by 2832
Abstract
Plasma cell leukemia (PCL) is a rare and highly aggressive plasma cell dyscrasia characterized by the presence of clonal circulating plasma cells in peripheral blood. PCL accounts for approximately 2–4% of all multiple myeloma (MM) cases. PCL can be classified in primary PCL [...] Read more.
Plasma cell leukemia (PCL) is a rare and highly aggressive plasma cell dyscrasia characterized by the presence of clonal circulating plasma cells in peripheral blood. PCL accounts for approximately 2–4% of all multiple myeloma (MM) cases. PCL can be classified in primary PCL (pPCL) when it appears de novo and in secondary PCL (sPCL) when it arises from a pre-existing relapsed/refractory MM. Despite the improvement in treatment modalities, the prognosis remains very poor. There is growing evidence that pPCL is a different clinicopathological entity as compared to MM, although the mechanisms underlying its pathogenesis are not fully elucidated. The development of new high-throughput technologies, such as microarrays and new generation sequencing (NGS), has contributed to a better understanding of the peculiar biological and clinical features of this disease. Relevant information is now available on cytogenetic alterations, genetic variants, transcriptome, methylation patterns, and non-coding RNA profiles. Additionally, attempts have been made to integrate genomic alterations with gene expression data. However, given the low frequency of PCL, most of the genetic information comes from retrospective studies with a small number of patients, sometimes leading to inconsistent results. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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20 pages, 1251 KiB  
Review
Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia
by Claudia Fiñana, Noel Gómez-Molina, Sandra Alonso-Moreno and Laura Belver
Cancers 2022, 14(5), 1335; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051335 - 04 Mar 2022
Cited by 7 | Viewed by 3965
Abstract
Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm of early childhood. Most of JMML patients experience an aggressive clinical course of the disease and require hematopoietic stem cell transplantation, which is currently the only curative treatment. JMML is characterized by RAS signaling [...] Read more.
Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm of early childhood. Most of JMML patients experience an aggressive clinical course of the disease and require hematopoietic stem cell transplantation, which is currently the only curative treatment. JMML is characterized by RAS signaling hyperactivation, which is mainly driven by mutations in one of five genes of the RAS pathway, including PTPN11, KRAS, NRAS, NF1, and CBL. These driving mutations define different disease subtypes with specific clinico-biological features. Secondary mutations affecting other genes inside and outside the RAS pathway contribute to JMML pathogenesis and are associated with a poorer prognosis. In addition to these genetic alterations, JMML commonly presents aberrant epigenetic profiles that strongly correlate with the clinical outcome of the patients. This observation led to the recent publication of an international JMML stratification consensus, which defines three JMML clinical groups based on DNA methylation status. Although the characterization of the genomic and epigenomic landscapes in JMML has significantly contributed to better understand the molecular mechanisms driving the disease, our knowledge on JMML origin, cell identity, and intratumor and interpatient heterogeneity is still scarce. The application of new single-cell sequencing technologies will be critical to address these questions in the future. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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23 pages, 2041 KiB  
Review
The Genomics of Hairy Cell Leukaemia and Splenic Diffuse Red Pulp Lymphoma
by David Oscier, Kostas Stamatopoulos, Amatta Mirandari and Jonathan Strefford
Cancers 2022, 14(3), 697; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030697 - 29 Jan 2022
Cited by 8 | Viewed by 3015
Abstract
Classical hairy cell leukaemia (HCLc), its variant form (HCLv), and splenic diffuse red pulp lymphoma (SDRPL) constitute a subset of relatively indolent B cell tumours, with low incidence rates of high-grade transformations, which primarily involve the spleen and bone marrow and are usually [...] Read more.
Classical hairy cell leukaemia (HCLc), its variant form (HCLv), and splenic diffuse red pulp lymphoma (SDRPL) constitute a subset of relatively indolent B cell tumours, with low incidence rates of high-grade transformations, which primarily involve the spleen and bone marrow and are usually associated with circulating tumour cells characterised by villous or irregular cytoplasmic borders. The primary aim of this review is to summarise their cytogenetic, genomic, immunogenetic, and epigenetic features, with a particular focus on the clonal BRAFV600E mutation, present in most cases currently diagnosed with HCLc. We then reflect on their cell of origin and pathogenesis as well as present the clinical implications of improved biological understanding, extending from diagnosis to prognosis assessment and therapy response. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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24 pages, 717 KiB  
Review
Recent Advances in the Genetic of MALT Lymphomas
by Juan José Rodríguez-Sevilla and Antonio Salar
Cancers 2022, 14(1), 176; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14010176 - 30 Dec 2021
Cited by 14 | Viewed by 5364
Abstract
Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances [...] Read more.
Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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21 pages, 1723 KiB  
Review
Near-Haploidy and Low-Hypodiploidy in B-Cell Acute Lymphoblastic Leukemia: When Less Is Too Much
by Oscar Molina, Alex Bataller, Namitha Thampi, Jordi Ribera, Isabel Granada, Pablo Velasco, José Luis Fuster and Pablo Menéndez
Cancers 2022, 14(1), 32; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14010032 - 22 Dec 2021
Cited by 10 | Viewed by 4196
Abstract
Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-cell acute lymphoblastic leukemia (B-ALL). This condition can be classified based on modal chromosome number as low-hypodiploidy (30–39 chromosomes) and near-haploidy (24–29 chromosomes), with unique cytogenetic and mutational landscapes. Hypodiploid B-ALL [...] Read more.
Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-cell acute lymphoblastic leukemia (B-ALL). This condition can be classified based on modal chromosome number as low-hypodiploidy (30–39 chromosomes) and near-haploidy (24–29 chromosomes), with unique cytogenetic and mutational landscapes. Hypodiploid B-ALL with <40 chromosomes has an extremely poor outcome, with 5-year overall survival rates below 50% and 20% in childhood and adult B-ALL, respectively. Accordingly, this genetic feature represents an adverse prognostic factor in B-ALL and is associated with early relapse and therapy refractoriness. Notably, half of all patients with hypodiploid B-ALL with <40 chromosomes cases ultimately exhibit chromosome doubling of the hypodiploid clone, resulting in clones with 50–78 chromosomes. Doubled clones are often the major clones at diagnosis, leading to “masked hypodiploidy”, which is clinically challenging as patients can be erroneously classified as hyperdiploid B-ALL. Here, we summarize the main cytogenetic and molecular features of hypodiploid B-ALL subtypes, and provide a brief overview of the diagnostic methods, standard-of-care treatments and overall clinical outcome. Finally, we discuss molecular mechanisms that may underlie the origin and leukemogenic impact of hypodiploidy and may open new therapeutic avenues to improve survival rates in these patients. Full article
(This article belongs to the Special Issue Genomics of Rare Hematologic Cancers)
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