Abstract
BackgroundLeukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. Studies regarding the detection of LSCs and the development of novel therapies for targeting them are extensive. The identification of LSCs and targeting therapies for them has been continuously under investigation.MethodsWe examined the levels of CD45dimCD34+CD38−CD133+ cells in bone marrow samples from patients with hematological malignancies and healthy controls, using four-color flow cytometry.ResultsInterestingly, the CD45dimCD34+CD38−CD133+ cells were highly expressed in the bone marrow of patients with AML compared to that in healthy controls (HC). Moreover, the proportions of CD45dimCD34+CD38−CD133+ cells were also examined in diverse hematological malignancies, including AML, CML, DLBCL, MM, MDS, HL, ALL, and CLL. LSCs were prominently detected in the BMCs isolated from patients with AML and CML, but rarely in BMCs isolated from patients with DLBCL, MM, MDS, ALL, CLL, and HL. Additionally, the high CD45dimCD34+CD38−CD133+ cell counts in AML patients served as a significantly poor risk factor for overall and event free survival.ConclusionsTherefore, our results suggest that CD45dimCD34+CD38−CD133+ cells in AML might potentially serve as LSCs. In addition, this cell population might represent a novel therapeutic target in AML.
Highlights
Leukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML
Patient samples We analyzed bone marrow samples collected from 87 patients who were newly diagnosed with AML (n = 40), chronic myeloid leukemia (CML, n = 6), diffuse large Bcell lymphoma (DLBCL, n = 19), multiple myeloma (MM, n = 10), myelodysplastic syndrome (MDS, n = 5), Hodgkin lymphoma (HL, n = 4), acute lymphocytic leukemia (ALL, n = 3), or chronic lymphocytic leukemia (CLL, n = 2)
A total of 40 AML patients were examined for the expression of the target antigens, CD45dimCD34+CD38−CD133+ on the surface of bone marrow cells (BMCs)
Summary
Leukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. The proportions of CD45dimCD34+CD38−CD133+ cells were examined in diverse hematological malignancies, including AML, CML, DLBCL, MM, MDS, HL, ALL, and CLL. Acute myeloid leukemia (AML) is generally regarded as a stem cell disease. It originates from a class of leukemic stem cells that are capable of self-renewal [1, 2]. The leukemia stem cells (LSCs) in AML play an important role in the development, relapse and progression of leukemia, and in the development of chemotherapeutic drug resistance in AML [5]. Rhenen et al showed that a high percentage of CD34+CD38− stem cells at diagnosis significantly correlated with a high minimal residual disease frequency and subsequently to relapse in AML patients
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