Bing Li1,2, John O Mascarenhas3, Raajit K Rampal4. 1. Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 443, New York, NY, 10022, USA. 2. MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. 3. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 443, New York, NY, 10022, USA. Rampalr@mskcc.org.
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. 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.
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. 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.
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