Erythroid Predominance in Bone Marrow Biopsies of Acute Myeloid Leukemia Patients after Decitabine Treatment Correlates with Mutation Profile and Complete Remission

Pathobiology. 2024;91(5):326-337. doi: 10.1159/000538953. Epub 2024 Apr 20.

Abstract

Introduction: Acute myeloid leukemia (AML) patients may receive hypomethylating agents such as decitabine (DAC) as part of their treatment. Not all patients respond to this therapy, and if they do, the clinical response may occur only after 3-6 courses of treatment. Hence, early biomarkers predicting response would be very useful.

Methods: We retrospectively analyzed a cohort of 22 AML patients who were treated with DAC. Histology of the bone marrow biopsy, pathogenic mutations, and methylation status were related to the treatment response.

Results: In 8/22 (36%) patients, an erythroid dominant response (EDR) pattern, defined as a ratio of myeloid cells/erythroid cells <1, was observed. In the remaining 14 cases, a myeloid predominance was preserved during treatment. No difference in the hypomethylating effect of DAC treatment was observed in patients with and without EDR, as global 5-methylcytosine levels dropped similarly in both groups. Mutational analysis by NGS using a panel of commonly mutated genes in AML showed that patients with an early EDR harbored on average less mutations, with U2AF1 mutations occurring more frequently, whereas RUNX1 mutations were underrepresented compared to non-EDR cases. Interestingly, the development of an EDR correlated with complete remission (7/8 cases with an EDR vs. only 2/14 cases without an EDR).

Conclusion: We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.

Keywords: Acute myeloid leukemia; Bone marrow biopsy; Decitabine; Erythroid hyperplasia.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use
  • Azacitidine / therapeutic use
  • Biopsy
  • Bone Marrow* / pathology
  • DNA Methylation
  • Decitabine* / therapeutic use
  • Female
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Remission Induction*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Decitabine
  • Antimetabolites, Antineoplastic
  • Azacitidine