Subclones of Bone Marrow CD34+ Cells in Acute Myeloid Leukemia at Diagnosis Confer Responses of Patients to Induction Chemotherapy

Background: Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy which has a prognosis that varies with genetic heterogeneity of its hematopoietic stem/progenitor cells(HSCPs). Intensive induction chemotherapy with cytarabine and anthracycline has been the standard of care for newly diagnosed AML, but about 30% of patients have no response to this regimen. The resistance mechanisms require deeper understanding. Methods In our study, using 10× Genomics, a high-throughput single cell RNA sequencing (scRNA-seq) platform, we analyzed the cellular heterogeneity of bone marrow CD34 + cells from newly diagnosed AML patients who were then divided into sensitive and resistant groups according to their responses to induction chemotherapy with cytarabine and anthracycline. ScRNA-seq data for healthy controls were obtained from the GEO database. We verified our findings by the TCGA database, GEO datasets and the multiparameter flow cytometry.ResultsFrom the integrative analysis of 60,402 cells, we established a landscape for single-cell CD34 + cells in AML patients and identified the hematopoietic stem/progenitor cell types based on the lineage signature genes. Interestingly, through recognizing the malignant-like clusters and comparing “resistant group” with “sensitive group”, we found a cell population with specific gene signatures ( CRIP1 high LGALS1 high S100A s high ) showing features of granulocyte-monocyte progenitors (GMP) was associated with poor prognosis of AML. And two cell populations of AML CD34 + cells marked by CD52 + or CD74 + DAP12 + were related to good response of patients to induction therapy, showing characteristics of hematopoietic stem cell (HSC). ConclusionOur study indicates the heterogeneity of AML CD34 + cells confers for outcomes of AML and provides possible biomarkers to predict the response of AML patients to induction chemotherapy.