Leukemic transformation of myeloproliferative neoplasms: Therapeutic and genomic considerations Journal Article
| Authors: | Li, B.; Mascarenhas, J. O.; Rampal, R. K. |
| Article Title: | Leukemic transformation of myeloproliferative neoplasms: Therapeutic and genomic considerations |
| Abstract: | Purpose of Review: Although BCR-ABL1-negative myeloproliferative neoplasms (MPN) are chronic, clonal hematopoietic stem cell (HSC) disorders marked by proliferation of one or more myeloid lineages, a substantial proportion of patients transform to acute myeloid leukemia. Leukemic transformation (LT) from a pre-existing MPN carries a dismal prognosis. Here, we review recent genetic, biological, and clinical data regarding LT. Recent Findings: In the last decade, DNA sequencing has revolutionized our understanding of the genomic landscape of LT. Mutations in TP53, ASXL1, EZH2, IDH1/2, and SRSF2 are significantly associated with increased risk of LT of MPNs. Preclinical modeling of these mutations is underway and has yielded important biological insights, some of which have therapeutic implications. Summary: Recent progress has led to the identification of recurrent genomic alterations in patients with LT. This has allowed mechanistic and therapeutic insight into the process of LT. In turn, this may lead to more mechanism-based therapeutic strategies that may improve patient outcomes. © 2018, Springer Science+Business Media, LLC, part of Springer Nature. |
| Keywords: | controlled study; treatment outcome; gene mutation; antianemic agent; janus kinase 2; review; nonhuman; mouse; protein p53; dna methylation; risk factor; cancer inhibition; splenomegaly; dna sequence; loss of function mutation; leukocytosis; myeloproliferative neoplasm; mouse model; asxl1 gene; ezh2 gene; extramedullary hematopoiesis; idh1 gene; myeloproliferative neoplasms; tp53 gene; aplasia; decitabine; ruxolitinib; leukemic transformation; srsf2 gene |
| Journal Title: | Current Hematologic Malignancy Reports |
| Volume: | 13 |
| Issue: | 6 |
| ISSN: | 1558-8211 |
| Publisher: | Springer |
| Date Published: | 2018-12-01 |
| Start Page: | 588 |
| End Page: | 595 |
| Language: | English |
| DOI: | 10.1007/s11899-018-0491-5 |
| PROVIDER: | scopus |
| PUBMED: | 30353413 |
| DOI/URL: | |
| Notes: | Curr. Hematol. Malig. Rep. -- Export Date: 2 January 2019 -- Review -- Source: Scopus C2 - 30353413 |
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