Abstract
CD9 is a cell surface protein and belongs to the tetraspanin family. Its role in carcinomagenesis has been widely studied in solid tumors but remains controversial, depending on the cancer type. Although CD9 seems to be associated with unfavorable outcome and disease progression in acute lymphoblastic leukemia (ALL), this marker has not yet been studied in acute myeloid leukemia (AML). First, we explored its prognostic role and its association with biological factors in a cohort of 112 AML patients treated with intensive chemotherapy. CD9 was expressed in 40% of AML and was associated with a favorable outcome (event‐free survival and relapse‐free survival) in univariate (P = 0.009 and P = 0.048, respectively) and multivariate (P = 0.004 and P = 0.039, respectively) analyses. Interestingly, CD9 expression was different between the more immature physiologic and AML cells (CD34+CD38−) as it was also expressed in AML on putative leukemic stem cells (LSCs) but not on hematopoietic stem cells (HSCs). Hence, CD9 could be a very relevant marker for minimal residual disease (MRD) monitoring in AML based on LSC targeting.
Highlights
Acute myeloid leukemia (AML) is the most common cause of leukemia‐related mortality in adult patients with a 5‐year overall survival (OS) around 40%.1 Initially, AML is a clonal disorder of hematopoietic stem cells (HSCs) characterized by an arrest of differentiation with associated proliferation, a subsequent accumulation of blast cells at various stages of incomplete maturation, and a reduced production of healthy hematopoietic elements
Detection by multiparametric flow cytometry (MFC) of markers expressed in blast cells is one of the most studied field over the past few years but identification of a cell antigen only expressed in AML has not been successful so far
CD9 is expressed in 40% of AML and, considering its expression at a significant level on leukemic stem cells (LSCs), it should be investigated when these cells are studied by the minimal residual disease (MRD) strategy that we described previously.[11]
Summary
Acute myeloid leukemia (AML) is the most common cause of leukemia‐related mortality in adult patients with a 5‐year overall survival (OS) around 40%.1 Initially, AML is a clonal disorder of hematopoietic stem cells (HSCs) characterized by an arrest of differentiation with associated proliferation, a subsequent accumulation of blast cells at various stages of incomplete maturation, and a reduced production of healthy hematopoietic elements. Over the past few years, various markers have been described to better characterize LSC or blast cells from AML with normal cytogenetics (CN‐AML) for minimal residual disease (MRD) monitoring.[7,8,9,10] targeting MRD. We analyzed the expression of CD9 on AML primary cells and physiologic progenitors, the prognostic role of CD9 on survival in AML patients treated with intensive chemotherapy, its association with classical biological factors and its usefulness to discriminate LSCs from HSCs
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