engleski

Decresed expression of bone morphogenetic proteins in acute promyelocytic leukemia correlates with molecular remission

Bone morphogenetic proteins (BMPs) belong to the TGFb superfamily of molecules and have important regulatory roles in embryonic morphogenesis and development, as well as in cell growth and differentiation in various cell types, including hematopoietic tissue. In the present study we investigated the expression of BMPs and BMP receptors in human leukemic bone marrow, using the model of acute promyelocytic leukemia (APL). RT-PCR assay was designed to detect the transcripts of BMP-2, -4, and -7, as well as of BMP receptors IA, IB, and II, before and after the treatment with all-trans retinoic acid (ATRA) in combination with chemotherapy. RNA was extracted after minimal manipulation from the bone marrow of four patients at the time of diagnosis and at the time of hematological marrow evaluation required by the treatment protocol. BMP-2, -4, and -7 were expressed in the marrow of leukemic samples, but were undetectable in molecularly confirmed remission samples. Morphological response, i.e. reduction of pathological cells without molecular clearance, was not sufficient for the inhibition of BMPs expression. There was a clear correlation between the BMPs expression and the expression of oncogenic fusion gene transcripts PML-RARa. When the minimal residual disease was detectable, expression of BMPs was also found. BMP receptors were expressed in the marrow samples but was not well correlated to the disease phase. Further research into the nature and cause of the relation of BMPs to the oncogene, and the evaluation of BMPs as possible minimal residual disease markers is warranted.

acute promyelocytic leukemia; retinoic acid; bone morphogenetic proteins

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