Abstract
Chronic Myeloid leukemia (CML) is a disorder causing uncontrolled growth of myeloproliferative blast cells. Tyrosine kinase inhibitors are not really useful in advanced stages and have their own side effects, reactions and resistance as well. Till date, CML can be fully cured only by bone marrow transplantation (BMT) which has its own limitations and thus need further studies to increase better survival of CML patients by this procedure. Our lab at Jaslok Hospital has been working on studying and characterizing mesenchymal stem cells in various types of hematological malignancies. We came up with a concept of isolating and characterizing mesenchymal stem cells (MSCs) from peripheral blood of a CML patient which can be used in combination with Bone Marrow Transplantation in the same CML patient. Our study has shown that the stem cells derived from peripheral blood of CML patient were found to be BCR/ABL -ve . We designated this cell line as a “BCR/ABL -ve ” cell line. Molecular characterization of these cells further confirmed their Mesenchymal phenotypes with distinct expression of CD105, CD13 and CD73 genes. Interestingly these cells also expressed pluripotency genes such as OCT4 and NANOG and cytokines i.e. IL6 and TNFα. We further confirmed the normal phenotype of BCR/ABL -ve MSCs by localizing expression of H-Ras, Rb, P53, P16, P21, and EGFR and Ki67 cancer related proteins in these cells by immunofluorescence Microscopy and by in vitro transformation assay. Thus, we suggest that these normal BCR/ABL -ve MSCs derived from CML patient’s peripheral blood can be used in addition to BMT procedure for a better recovery of CML disease in near future.
Highlights
Chronic Myeloid leukemia (CML) is a disorder of the myeloid lineage [1]
As Chronic Myeloid Leukemia (CML) has the characteristic fusion of BCR/ ABL gene, we considered detecting these cells for BCR/ABL transcript and profile them for some common oncogenic markers
Isolation of mesenchymal stem cells from peripheral blood of CML patient The cells suspended in above growth media were incubated at 37°C with 5% CO2 at 90% humidity in CO2 incubator as described above
Summary
Chronic Myeloid leukemia (CML) is a disorder of the myeloid lineage [1]. It accounts for almost 15% of all adult leukemias. The disease progresses through three major stages i.e. chronic phase, accelerated phase and blast crisis phase which is decided on the number of blasts cells present in the patient’s blood. In most cases the reciprocal translocation mutation t[9:22] known as Philadelphia chromosome results in a constitutively increase in tyrosine kinase activity due to this fusion BCR/ABL gene protein [3]. This constitutive expression of the fusion gene is the central target of this disease. Bone Marrow Transplant (BMT) remains as the only known cure for this disease [9] but, it has its own limitations
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