Leukemia secondary to myeloproliferative neoplasms.
Abnormal Karyotype
Allografts
Antineoplastic Agents
/ therapeutic use
Cell Transformation, Neoplastic
Chromosome Aberrations
Clonal Evolution
Combined Modality Therapy
Comorbidity
Disease Progression
Drug Resistance, Neoplasm
Drugs, Investigational
/ therapeutic use
Genes, Neoplasm
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
/ etiology
Models, Biological
Mutation
Myeloproliferative Disorders
/ genetics
Neoplasm Proteins
/ genetics
Recurrence
Risk Factors
Single-Cell Analysis
Therapies, Investigational
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
02 07 2020
02 07 2020
Historique:
received:
11
09
2019
accepted:
23
01
2020
pubmed:
21
5
2020
medline:
18
2
2021
entrez:
21
5
2020
Statut:
ppublish
Résumé
Secondary acute myeloid leukemias (AMLs) evolving from an antecedent myeloproliferative neoplasm (MPN) are characterized by a unique set of cytogenetic and molecular features distinct from de novo AML. Given the high frequency of poor-risk cytogenetic and molecular features, malignant clones are frequently insensitive to traditional AML chemotherapeutic agents. Allogeneic stem cell transplant, the only treatment modality shown to have any beneficial long-term outcome, is often not possible given the advanced age of patients at time of diagnosis and frequent presence of competing comorbidities. Even in this setting, relapse rates remain high. As a result, outcomes are generally poor and there remains a significant unmet need for novel therapeutic strategies. Although advances in cancer genomics have dramatically enhanced our understanding of the molecular events governing clonal evolution in MPNs, the cell-intrinsic and -extrinsic mechanisms driving leukemic transformation at this level remain poorly understood. Here, we review known risk factors for the development of leukemic transformation in MPNs, recent progress made in our understanding of the molecular features associated with leukemic transformation, current treatment strategies, and emerging therapeutic options for this high-risk myeloid malignancy.
Identifiants
pubmed: 32430500
pii: S0006-4971(20)61917-6
doi: 10.1182/blood.2019000943
pmc: PMC7332899
doi:
Substances chimiques
Antineoplastic Agents
0
Drugs, Investigational
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
61-70Subventions
Organisme : NCI NIH HHS
ID : P01 CA108671
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2020 by The American Society of Hematology.
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