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Blood Apr 2017RUNX1 is a member of the core-binding factor family of transcription factors and is indispensable for the establishment of definitive hematopoiesis in vertebrates. is... (Review)
Review
RUNX1 is a member of the core-binding factor family of transcription factors and is indispensable for the establishment of definitive hematopoiesis in vertebrates. is one of the most frequently mutated genes in a variety of hematological malignancies. Germ line mutations in cause familial platelet disorder with associated myeloid malignancies. Somatic mutations and chromosomal rearrangements involving are frequently observed in myelodysplastic syndrome and leukemias of myeloid and lymphoid lineages, that is, acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myelomonocytic leukemia. More recent studies suggest that the wild-type is required for growth and survival of certain types of leukemia cells. The purpose of this review is to discuss the current status of our understanding about the role of RUNX1 in hematological malignancies.
Topics: Acute Disease; Animals; Chromosome Aberrations; Chronic Disease; Core Binding Factor Alpha 2 Subunit; Hematologic Neoplasms; Humans; Leukemia; Myelodysplastic Syndromes; Neoplasm Proteins
PubMed: 28179279
DOI: 10.1182/blood-2016-10-687830 -
British Journal of Haematology Dec 2022Despite the success of BCR-ABL-specific tyrosine kinase inhibitors (TKIs) such as imatinib in chronic phase (CP) chronic myeloid leukaemia (CML), patients with blast... (Review)
Review
Despite the success of BCR-ABL-specific tyrosine kinase inhibitors (TKIs) such as imatinib in chronic phase (CP) chronic myeloid leukaemia (CML), patients with blast phase (BP)-CML continue to have a dismal outcome with median survival of less than one year from diagnosis. Thus BP-CML remains a critical unmet clinical need in the management of CML. Our understanding of the biology of BP-CML continues to grow; genomic instability leads to acquisition of mutations which drive leukaemic progenitor cells to develop self-renewal properties, resulting in differentiation block and a poor-prognosis acute leukaemia which may be myeloid, lymphoid or bi-phenotypic. Similar advances in therapy are urgently needed to improve patient outcomes; however, this is challenging given the rarity and heterogeneity of BP-CML, leading to difficulty in designing and recruiting to prospective clinical trials. This review will explore the treatment of BP-CML, evaluating the data for TKI therapy alone, combinations with intensive chemotherapy, the role of allogeneic haemopoietic stem cell transplantation, the use of novel agents and clinical trials, as well as discussing the most appropriate methods for diagnosing BP and assessing response to therapy, and factors predicting outcome.
Topics: Humans; Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Prospective Studies; Imatinib Mesylate; Protein Kinase Inhibitors
PubMed: 35866251
DOI: 10.1111/bjh.18370 -
Annals of Oncology : Official Journal... Jan 2021
Topics: Follow-Up Studies; Humans; Leukemia, Lymphocytic, Chronic, B-Cell
PubMed: 33091559
DOI: 10.1016/j.annonc.2020.09.019 -
Annals of Hematology Aug 2023Myeloid sarcoma (MS) is a distinct entity among myeloid neoplasms defined as a tumour mass of myeloid blasts occurring at an anatomical site other than the bone marrow,... (Review)
Review
Myeloid sarcoma (MS) is a distinct entity among myeloid neoplasms defined as a tumour mass of myeloid blasts occurring at an anatomical site other than the bone marrow, in most cases concomitant with acute myeloid leukaemia (AML), rarely without bone marrow involvement. MS may also represent the blast phase of chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). However, the clinical and molecular heterogeneity of AML, as highlighted by the 2022 World Health Organization (WHO) and International Consensus (ICC) classifications, indirectly define MS more as a set of heterogeneous and proteiform diseases, rather than a homogeneous single entity. Diagnosis is challenging and relies mainly on histopathology, immunohistochemistry, and imaging. Molecular and cytogenetic analysis of MS tissue, particularly in isolated cases, should be performed to refine the diagnosis, and thus assign prognosis guiding treatment decisions. If feasible, systemic therapies used in AML remission induction should be employed, even in isolated MS. Role and type of consolidation therapy are not univocally acknowledged, and systemic therapies, radiotherapy, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) should be considered. In the present review, we discuss recent information on MS, focusing on diagnosis, molecular findings, and treatments also considering targetable mutations by recently approved AML drugs.
Topics: Humans; Sarcoma, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Hematopoietic Stem Cell Transplantation
PubMed: 37286874
DOI: 10.1007/s00277-023-05288-1 -
Nature Reviews. Cancer Mar 2020For two decades, leukaemia stem cells (LSCs) in chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem cell... (Review)
Review
For two decades, leukaemia stem cells (LSCs) in chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem cell field. In CML, the acquisition of the fusion tyrosine kinase BCR-ABL1 in a haematopoietic stem cell drives its transformation to become a LSC. In AML, LSCs can arise from multiple cell types through the activity of a number of oncogenic drivers and pre-leukaemic events, adding further layers of context and genetic and cellular heterogeneity to AML LSCs not observed in most cases of CML. Furthermore, LSCs from both AML and CML can be refractory to standard-of-care therapies and persist in patients, diversify clonally and serve as reservoirs to drive relapse, recurrence or progression to more aggressive forms. Despite these complexities, LSCs in both diseases share biological features, making them distinct from other CML or AML progenitor cells and from normal haematopoietic stem cells. These features may represent Achilles' heels against which novel therapies can be developed. Here, we review many of the similarities and differences that exist between LSCs in CML and AML and examine the therapeutic strategies that could be used to eradicate them.
Topics: Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Disease Management; Disease Susceptibility; Drug Development; History, 20th Century; History, 21st Century; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Neoplastic Stem Cells; Research
PubMed: 31907378
DOI: 10.1038/s41568-019-0230-9 -
Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Annals of Oncology : Official Journal... Jul 2017
Topics: Follow-Up Studies; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Medical Oncology
PubMed: 28881915
DOI: 10.1093/annonc/mdx219 -
Blood Reviews Jul 2023Large Granular Lymphocyte (LGL) Leukemia is a rare, heterogeneous even more that once thought, chronic lymphoproliferative disorder characterized by the clonal expansion... (Review)
Review
Large Granular Lymphocyte (LGL) Leukemia is a rare, heterogeneous even more that once thought, chronic lymphoproliferative disorder characterized by the clonal expansion of T- or NK-LGLs that requires appropriate immunophenotypic and molecular characterization. As in many other hematological conditions, genomic features are taking research efforts one step further and are also becoming instrumental in refining discrete subsets of LGL disorders. In particular, STAT3 and STAT5B mutations may be harbored in leukemic cells and their presence has been linked to diagnosis of LGL disorders. On clinical grounds, a correlation has been established in CD8+ T-LGLL patients between STAT3 mutations and clinical features, in particular neutropenia that favors the onset of severe infections. Revisiting biological aspects, clinical features as well as current and predictable emerging treatments of these disorders, we will herein discuss why appropriate dissection of different disease variants is needed to better manage patients with LGL disorders.
Topics: Humans; Leukemia, Large Granular Lymphocytic; Killer Cells, Natural; Mutation; Leukemia; Neutropenia
PubMed: 36870881
DOI: 10.1016/j.blre.2023.101058 -
Acta Haematologica 2018In 1963 Jean Bernard introduced the concept of "geographic hematology" and distinguished 2 branches, i.e., "ethnic hematology," which deals with differences between... (Review)
Review
In 1963 Jean Bernard introduced the concept of "geographic hematology" and distinguished 2 branches, i.e., "ethnic hematology," which deals with differences between populations, and "environmental hematology," which considers factors such as food habits, infections, and others. Both of these branches have implications in the distribution of hematological diseases worldwide. In comparison with Caucasian populations, in Mexico a significantly higher prevalence of acute lymphoblastic, acute promyelocytic, and acute megakaryoblastic leukemias has been described. The rate of chronic myeloid leukemia seems to be as high as that reported in Caucasian populations, while other myeloproliferative neoplasias are significantly less frequent in Mexico. Significantly lower prevalences of hairy cell leukemia, chronic lymphocytic leukemia, multiple myeloma, and Waldenström's macroglobulinemia have been reported from Mexico. Regrettably, the influence of drug companies interested in selling their new and expensive drugs has resulted in both overdiagnosis of some diseases and overidentification of the refractory forms of some of these conditions to justify the use of unnecessary drugs.
Topics: Hematologic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Mexico; Myeloproliferative Disorders; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prevalence; Thalassemia
PubMed: 30227427
DOI: 10.1159/000491989 -
Experimental Hematology Feb 2022The CD99 gene encodes a transmembrane protein that is involved in cell differentiation, adhesion, migration, and protein trafficking. CD99 is differentially expressed on... (Review)
Review
The CD99 gene encodes a transmembrane protein that is involved in cell differentiation, adhesion, migration, and protein trafficking. CD99 is differentially expressed on the surface of hematopoietic cells both in the myeloid and lymphoid lineages. CD99 has two isoforms, the long and short isoforms that play different roles depending on the cellular context. There has been extensive evidence supporting the role of CD99 in myeloid and lymphoblastic leukemias. Here we review research findings related to the CD99 in malignant hematopoiesis. We also summarize the significance of CD99 as a therapeutic target in hematological malignancies.
Topics: 12E7 Antigen; Animals; Gene Expression Regulation, Leukemic; Hematopoiesis; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 34920053
DOI: 10.1016/j.exphem.2021.12.363 -
Clinical Medicine (London, England) May 2022Lymphocytosis is a common blood-test finding. Establishing whether the cause of lymphocytosis is benign or malignant is key to managing patients appropriately. A...
Lymphocytosis is a common blood-test finding. Establishing whether the cause of lymphocytosis is benign or malignant is key to managing patients appropriately. A lymphocytosis should always prompt clinical review including a thorough history, examination and appropriate preliminary investigations (blood tests, blood film). The majority of patients with chronic lymphocytic leukaemia (CLL) present incidentally due to a lymphocytosis found on routine blood tests. Patient outcomes vary considerably based on genetic pre-disposition and various prognostic markers (age, Binet or Rai staging, and B2-microglobulin). Although not curative, chemo-immunotherapy is an effective treatment strategy for the majority of CLL patients with progressive disease. More recently, novel oral therapies have been developed that target key signalling and apoptosis pathways and that are being used in relapse settings and as first-line treatments for certain patients.
Topics: Humans; Immunotherapy; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytosis; Neoplasm Recurrence, Local; Prognosis; Treatment Outcome
PubMed: 35584829
DOI: 10.7861/clinmed.2022-0150