Subclones of bone marrow CD34⁺ cells in acute myeloid leukemia at diagnosis confer responses of patients to induction chemotherapy.

Abstract

Acute myeloid leukemia (AML) is a hematopoietic malignancy with a prognosis that varies with genetic heterogeneity of hematopoietic stem/progenitor cells (HSPCs). Induction chemotherapy with cytarabine and anthracycline has been the standard care for newly diagnosed AML, but about 30% of patients have no response to this regimen. The resistance mechanisms require deeper understanding. In our study, using single-cell RNA sequencing, we analyzed the heterogeneity of bone marrow CD34⁺ cells from newly diagnosed patients with AML who were then divided into sensitive and resistant groups according to their responses to induction chemotherapy with cytarabine and anthracycline. We verified our findings by TCGA database, GEO datasets, and multiparameter flow cytometry. We established a landscape for AML CD34⁺ cells and identified HSPC types based on the lineage signature genes. Interestingly, we found a cell population with CRIP1^high LGALS1^high S100As^high showing features of granulocyte-monocyte progenitors was associated with poor prognosis of AML. And two cell populations marked by CD34⁺ CD52⁺ or CD34⁺ CD74⁺ DAP12⁺ were related to good response to induction therapy, showing characteristics of hematopoietic stem cells. Our study indicates the subclones of CD34⁺ cells confers for outcomes of AML and provides biomarkers to predict the response of patients with AML to induction chemotherapy.