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CD37 high expression as a potential biomarker and association with poor outcome in acute myeloid leukemia.

ABSTRACT: BACKGROUND:CD37, a member of the transmembrane 4 superfamilies (TM4SF), has been proved to be abnormally expressed in a range of malignancies. Herein, we investigate the effects of CD37 expression and analyze its clinical outcome in acute myeloid leukemia (AML) patients. METHODS:The RNA-seq and clinical data of AML patients were obtained from cBioPortal database. CD37 correlated genes, the expression prolife and survival curve of eight key genes were acquired from Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN. Pathway enrichment and protein-protein interaction (PPI) network analysis were performed based on metascape databases. RESULTS:Our results showed that CD37 mRNA expression level was significantly up-regulated in patients with AML compared with healthy persons. Patients with high CD37 expression had shorter overall survival (OS) and disease-free survival (DFS). Pathway analysis data showed that CD37 is involved in DNA replication, RNA transport, Salmonella infection, ribonucleoprotein complex biogenesis, cell cycle phase transition and so on. Furthermore, we found eight genes correlated with CD37 are all highly expressed in AML patients, and high expression is associated with poor prognosis. CONCLUSION:Our study described systematical expression profiles and the prognostic values of CD37 in AML; our data suggested CD37 might be novel therapeutic target and promising prognostic biomarker in the patients.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC7253400 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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CD37 high expression as a potential biomarker and association with poor outcome in acute myeloid leukemia.

Zhang Qi Q Han Qi Q Zi Jie J Song Chunhua C Ge Zheng Z

Bioscience reports 20200501 5

<h4>Background</h4>CD37, a member of the transmembrane 4 superfamilies (TM4SF), has been proved to be abnormally expressed in a range of malignancies. Herein, we investigate the effects of CD37 expression and analyze its clinical outcome in acute myeloid leukemia (AML) patients.<h4>Methods</h4>The RNA-seq and clinical data of AML patients were obtained from cBioPortal database. CD37 correlated genes, the expression prolife and survival curve of eight key genes were acquired from Gene Expression ...[more]

PMID: 32400873

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Project description:Hematologic responses to hypomethylating agents are often delayed in patients with myelodysplastic syndrome or acute myeloid leukemia. Fetal hemoglobin is a potential novel bio-marker of response: recently, we demonstrated that a high fetal hemoglobin level prior to decitabine treatment was associated with superior outcome. Here we investigated whether early fetal hemoglobin induction during decitabine treatment also had prognostic value, and studied the potential of decitabine to induce erythroid differentiation and fetal hemoglobin expression in vitro Fetal hemoglobin levels were measured by high-performance liquid chromatography in patients with higher-risk myelodysplastic syndrome (n=16) and acute myeloid leukemia (n=37) before treatment and after each course of decitabine. Levels above 1.0% were considered induced. Patients achieving complete or partial remission as best response had attained a median fetal hemoglobin of 1.9% after two courses of treatment, whereas the median value in patients who did not reach complete or partial remission was 0.8% (P=0.015). Fetal hemoglobin induction after two courses of decitabine treatment was associated with early platelet doubling (P=0.006), and its subsequent decrease with hematologic relapse. In patients with myelodysplastic syndrome, induction of fetal hemoglobin after course 2 of treatment was associated with longer overall survival: median of 22.9 versus 7.3 months in patients with or without induction of fetal hemoglobin, respectively [hazard ratio=0.2 (95% confidence interval: 0.1-0.9); P=0.03]. In vitro decitabine treatment of two bi-potential myeloid leukemia cell lines (K562 and HEL) resulted in induction of an erythroid (not megakaryocytic) differentiation program, and of fetal hemoglobin mRNA and protein, associated with GATA1 gene demethylation and upregulation. In conclusion, fetal hemoglobin may provide a useful dynamic biomarker during hypomethylating agent therapy in patients with myelodysplastic syndrome or acute myeloid leukemia.

Project description:IntroductionTreatment failure in acute myeloid leukemia is probably caused by the presence of leukemia initiating cells, also referred to as leukemic stem cells, at diagnosis and their persistence after therapy. Specific identification of leukemia stem cells and their discrimination from normal hematopoietic stem cells would greatly contribute to risk stratification and could predict possible relapses.ResultsFor identification of leukemic stem cells, we developed flow cytometric methods using leukemic stem cell associated markers and newly-defined (light scatter) aberrancies. The nature of the putative leukemic stem cells and normal hematopoietic stem cells, present in the same patient's bone marrow, was demonstrated in eight patients by the presence or absence of molecular aberrancies and/or leukemic engraftment in NOD-SCID IL-2R?-/- mice. At diagnosis (n=88), the frequency of the thus defined neoplastic part of CD34+CD38- putative stem cell compartment had a strong prognostic impact, while the neoplastic parts of the CD34+CD38+ and CD34- putative stem cell compartments had no prognostic impact at all. After different courses of therapy, higher percentages of neoplastic CD34+CD38- cells in complete remission strongly correlated with shorter patient survival (n=91). Moreover, combining neoplastic CD34+CD38- frequencies with frequencies of minimal residual disease cells (n=91), which reflect the total neoplastic burden, revealed four patient groups with different survival.Conclusion and perspectiveDiscrimination between putative leukemia stem cells and normal hematopoietic stem cells in this large-scale study allowed to demonstrate the clinical importance of putative CD34+CD38- leukemia stem cells in AML. Moreover, it offers new opportunities for the development of therapies directed against leukemia stem cells, that would spare normal hematopoietic stem cells, and, moreover, enables in vivo and ex vivo screening for potential efficacy and toxicity of new therapies.

Dataset Information

CD37 high expression as a potential biomarker and association with poor outcome in acute myeloid leukemia.

Publications

CD37 high expression as a potential biomarker and association with poor outcome in acute myeloid leukemia.

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