Journal
BONE MARROW TRANSPLANTATION
Volume 57, Issue 1, Pages 95-105Publisher
SPRINGERNATURE
DOI: 10.1038/s41409-021-01454-z
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Funding
- Ministry of Science and Technology (Taiwan) [MOST 104-2314-B-002-128-MY4, 106-2314-B-002-226-MY3]
- Ministry of Health and Welfare (Taiwan) [MOHW 107-TDU-B-211-114009]
- Department of Medical Research, National Taiwan University Hospital [NTUH 102P06]
- Taiwan Health Foundation
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The study found that FLT3-ITDlow in AML patients is associated with negative enrichment of leukemic stem cell features, marked enrichment of the RAS pathway, and higher frequencies of RAS pathway mutations, different from FLT3-ITDhigh. Concurrent CEBPA double mutations are favorable prognostic factors, while MLL-PTD and mutations in splicing factors are unfavorable prognostic factors in FLT3-ITDlow patients. Allo-HSCT in CR1 significantly prolongs overall survival and event-free survival in FLT3-ITDlow patients.
The mutant burden of FLT3-ITD modulates its prognostic impact on patients with acute myeloid leukemia (AML). However, for patients with low allelic ratio (AR) FLT3-ITD (FLT3-ITDlow, AR < 0.5), clinical features, as well as genomic and transcriptomic profiles remain unclear, and evidence supporting allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) remains controversial. This study aimed to elucidate the genomic features, prognosis, and transplantation outcome of FLT3-ITDIow in AML patients with intermediate-risk cytogenetics. FLT3-ITDlow was associated with a negative enrichment of the leukemic stem cell signature, a marked enrichment of the RAS pathway, and with higher frequencies of RAS pathway mutations, different from those with FLT3-ITDhigh. Concurrent CEBPA double mutations were favorable prognostic factors, whereas MLL-PTD, and mutations in splicing factors were unfavorable prognostic factors in FLT3-ITDlow patients. Patients with FLT3-ITDlow had a shorter overall survival (OS) and event-free survival (EFS) than those with FLT3(wt). Allo-HSCT in CR1 was associated with a significantly longer OS and EFS compared with postremission chemotherapy in patients with FLT3-ITDlow. In conclusion, FLT3-ITDlow is associated with different mutational and transcriptomic profiles compared with FLT3-ITDhigh. The presence of concomitant poor-risk mutations exert negative prognostic impacts in patients with FLT3-ITDlow, who markedly benefit from allo-HSCT in CR1.
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