Single-cell RNA sequencing of peripheral blood mononuclear cells from the patient with acute promyelocytic leukemia: a case study

Abstract

© Annals of Blood. All rights reserved. Ann Blood 2021;6:21 | http://dx.doi.org/10.21037/aob-20-65 Acute promyelocytic leukemia (APL), a special type of acute myeloid leukemia (AML, M3 subtype), is an aggressive hematological malignancy (1). APL occurs mostly in the young and middle-aged people, accounting for approximately 10% of the AML cases. It is characterized by the unrestricted proliferation of a large number of leukemia cells in bone marrow and other hematopoietic tissues, with the significantly inhibited hematopoietic function, causing the disease develops rapidly with the dangerous clinical manifestations (2). Bleeding and embolism are prone to occur during the progression of APL, which is the leading cause to the death of APL patients. APL used to be the myeloid leukemia with the highest fatality rate. With the in-depth research on the pathogenesis and therapy of APL, the survival rate of APL patients has been greatly improved under the treatment of retinoic acid (ATRA) and arsenic trioxide (As2O3) (3). However, the early mortality rate is still high since the bleeding and disseminated intravascular coagulation (DIC), the most prominent features of APL, causing the death in the early stage (4). Therefore, to control blood coagulation timely is the key to the treatment in the early stage of APL patients. The early effective intervention is bound to require the rapid and precise diagnosis of APL patients. However, the conventional diagnostic techniques of APL based on the genetics and morphology are still defective and unstable, such as occasional misdiagnosis and time-consuming. Single-cell RNA sequencing (scRNA-seq) is currently the most advanced technology in the field of precision medicine, with a very broad application prospect in the disease diagnosis (5). This method allows us to quickly and systematically assess the heterogeneity of various types of cells from the patient, identifying the disease-related cells and their genetic and phenotypic characteristics, especially for those few abnormal cells that occur in the early stage of the disease (6). Therefore, this method is particularly suitable for the early detection and companion diagnosis of diseases, such as APL. There have been some studies on the single-cell transcriptomics analysis in AML, but not in APL (7). In this study, we conducted the single-cell transcriptomics detection method based on the 10× Genomics Chromium droplet-based platform to evaluate the single-cell heterogeneity of peripheral blood mononuclear cells (PBMCs) from the APL patient, exploring the feasibility of scRNA-seq for the rapid and precise diagnosis of APL. The PBMCs was separated from the blood of one APL patient (female, 27 years old) after the patient’s consent and the approval of the ethics committee. This patient presented with skin ecchymosis for 1 month. The complete blood cell count (CBC) revealed was normal white blood cell count (WBC of 9.05×10/L), anemia (hemoglobin of 56 g/L) and thrombocytopenia (platelets 32×10/L). The bone marrow was hyperproliferative (mainly primitive granulocytes and neutrophils), which was consistent with the marrow image of AML. The single-cell transcriptomics Letter to the Editor