engleski

Bone morphogenetic proteins expression in acute promyelocytic leukemia correlates with molecular remission

Bone morphogenetic proteins (BMPs) belong to TGFb superfemily of cytokines with important regulatory roles in embryonic morphogenesis and development, cell growth and differentiation in various cell types including hematopoietic tissue. Recent studies using RNase protection assay found increased levels of gene expression for several BMPs in a panel of lymphatic leukemic cell lines. Low levels of BMP2 and 4 expression were seen in normal bone marrow. In the present study we investigated the expression of BMPs and BMP receptors in human leukemic bone marrow. A model of acute promyelocytic leukemia (APL) was selected. An RT-PCR assay was designed to detect the transcripts of BMP2, 4 and 7 as well the BMP receptors I, IA, and II before and after leukemia treatment with the differentiating agent All-trans retinoic acid (ATRA) in combination with chemotherapy. RNA was extracted after minimal manipulation from the bone marrow of four patients at diagnosis and at the points of hematological marrow evaluation as required by the treatment protocol. BMP 2, 4, and 7 were expressed in the leukemic marrow but they were undetectable in molecularly confirmed remission marrows (maximal sensitivity of the assay 1x10-5). Morphological response with the reduction of pathological cells but without molecular clearance was not sufficient. There was a clear correlation between the BMPs expression and expression of oncogenic fusion gene transcript PML-RARa. When the minimal residual disease was detectable BMPs were expressed too. BMP receptors expression could be detected in the marrows at all test points irrespective of the disease phase. A research into the nature and cause of the relation of BMPs to the oncogene and the evaluation of BMPs as possible minimal residual disease marker is needed.

Leukemia; acute promyelocytic; Bone Morphogenetic Proteins (BMP)

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