The molecular signature of AML mesenchymal stromal cells reveals candidate genes related to the leukemogenic process.
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by myeloid precursor proliferation in the bone marrow, apoptosis reduction and differentiation arrest. Although there are several studies in this field, events related to disease initiation and progression remain unknown. The malignant transformation of hematopoietic stem cells (HSC) is thought to generate leukemic stem cells, and this transformation could be related to changes in mesenchymal stromal cell (hMSC) signaling. Thus, the aim of this work was to analyze the gene expression profile of hMSC from AML patients (hMSC-AML) compared to healthy donors hMSCs (hMSC-HD). The results showed a common molecular signature for all hMSC-AML. Other assays were performed with a large number of patients and the results confirmed a molecular signature that is capable of distinguishing hMSC-AML from hMSC-HD. Moreover, CCL2 and BMP4 genes encode secreted proteins that could affect HSCs. To verify whether these proteins are differentially expressed in AML patients, ELISA was performed with plasma samples. CCL2 and BMP4 proteins are differentially expressed in AML patients, indicating changes in hMSC-AML signaling. Altogether, hMSCs-AML signaling alterations could be an important factor in the leukemic transformation process.
Stem Cell Laboratory, Bone Marrow Transplantation Unit, National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia Para o Controle do Câncer (INCT), Rio de Janeiro, RJ, Brazil. Electronic address: rbgomes@inca.gov.br.
Renata
R
Binato
Stem Cell Laboratory, Bone Marrow Transplantation Unit, National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia Para o Controle do Câncer (INCT), Rio de Janeiro, RJ, Brazil.
Nathalia Correa
NC
de Almeida Oliveira
Stem Cell Laboratory, Bone Marrow Transplantation Unit, National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia Para o Controle do Câncer (INCT), Rio de Janeiro, RJ, Brazil.
Barbara
B
Du Rocher
Stem Cell Laboratory, Bone Marrow Transplantation Unit, National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia Para o Controle do Câncer (INCT), Rio de Janeiro, RJ, Brazil.
Eliana
E
Abdelhay
D000293:Adolescent; D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002453:Cell Cycle; D049109:Cell Proliferation; D002648:Child; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D055815:Young Adult
Acute myeloid leukemia (AML); Human mesenchymal stromal cells (hMSCs); Molecular signature