AI Article Synopsis

  • * A study examined HIF-1α levels in the bone marrow of 29 newly diagnosed NPM1FLT3-ITD normal karyotype AML patients and found that over half exhibited strong HIF-1α expression, correlating this with increased relapse rates and shorter relapse-free survival (RFS).
  • * High HIF-1α levels might serve as a useful prognostic biomarker for predicting poor RFS and resistance to cytarabine in NPM1FLT

Article Abstract

Nucleophosmin1 (NPM1) mutated acute myeloid leukemia (AML) without FLT3-ITD mutation is classified as a favorable risk AML which responds well to cytarabine therapy. Hypoxia-inducible factor-1 alpha (HIF-1α) promotes leukemic cell survival and maintains leukemic stem cell quiescence possibly contributing to cytarabine resistance. This study evaluated HIF-1α expression using immunohistochemistry in bone marrow of 29 newly diagnosed NPM1FLT3-ITD normal karyotype AML patients and analyzed its correlation with survival. All patients achieved complete remission after standard induction chemotherapy and proceeded to cytarabine consolidations. Positive HIF-1α staining with golgi body pattern and strong cytoplasmic HIF-1α expression was identified in 34.5% and 58.6% of patients, respectively. The expression of golgi body or strong cytoplasmic HIF-1α expression was related to increased relapse (p = 0.048) with significantly inferior relapse-free survival (RFS, p = 0.042). Using multivariate analysis, extramedullary disease at diagnosis was revealed as an independent prognostic factor for adverse RFS (hazard ratio [HR] 3.82; 95% confidence interval [CI] 1.26-11.55, p = 0.018), while golgi body or strong cytoplasmic HIF-1α expression showed a trend toward poor RFS (HR 3.56; 95% CI 1.00-12.69, p = 0.050). In summary, high HIF-1α expression is potentially a baseline prognostic biomarker for poor RFS and cytarabine resistance in NPM1FLT3-ITD AML. Further studies with the large number of patients are warranted.

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Source
http://dx.doi.org/10.1007/s00277-024-06124-wDOI Listing

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