Expression Of Notch Signaling Pathway-related Genes In Chronic Myeloid Leukemia And Its Clinical Significance

Chronic myeloid leukemia is a hematological stem cell cloning disorder, more than 95% CML patients have Ph chromosome and(or) BCR- ABL fusion gene. The median survival time of patients with chronic myeloid leukemia is 3 to 5 years, the natural history of the disease is chronic phase, accelerated phase, and blast crisis. Chronic phase is relatively occult. When disease developing to accelerated phase/blast crisis, the disease's progression is quick and therapeutic effect is poor. Studies have shown that abnormal activation of Notch signaling pathways regulate stem cell proliferation, differentiation and decide the fate of the cells, and it may associate with the development of hematologic disorder. Our previous studies found that Notch gene can promote proliferation and engraftment of umbilical cord blood hematopoietic stem cells, Notch genes were involved in the proliferation of hematopoietic stem cells. In hematologic tumors, scholars have studied the expression and clinical significance of Notch signaling pathway-related genes in acute leukemia, lymphoma, chronic lymphocytic leukemia and other disorder, while the Notch signaling pathway-related genes in chronic myeloid leukemia research focused on cell lines and mice model. K562 cell line expresses Notch1-4 and Jagged2, intracellular fragment of Notch receptors or ligands inhibit K562 cell growth and induce apoptosis. BCR-ABL and Notch1 induces acute leukemia in a CML transgenic mouse. In mouse bone marrow transplantation model, Hes1 and BCR-ABL fusion genes work together to promote CML into blast crisis. The relationship between Notch signaling pathway-related genes and CML was not well studied, scholars mainly concentrated on animal experiment and vitro culture, but fewer researcher studied the expression level in CML patients.The study mainly discusses Notch signaling pathway-related genes expression level in the different clinical stages of the chronic myeloid leukemia patients and its clinical significance. The mononuclear cells from bone marrow of chronic myeloid leukemia patients(total 24 cases, include 12 cases chronic phase and 12 cases blast crisis), and healthy donors(9 cases) were collected, then the expression of Notch signaling pathway-related genes were detected respectively by real-time fluorescent quantitative PCR(qRT-PCR). The correlation of Notch signaling pathway-related genes with clinical parameters such as white blood cell count, hemoglobin, blood platelet count, BCR-ABL/ABL1 were analyzed. The expression levels of Notch1-2, Jagged1, Hes1 mRNA in CML were higher than those in control group(P<0.05), but there was no statistically significant difference of Delta-like1 m RNA expression level in CML and control group(P>0.05). The expression levels of Jagged1 and Hes1 mRNA in blast crisis were higher than those in chronic phase and the control group(P<0.05), but there was no statistically significant difference of Notch1, Notch2, Delta-like1 mRNA expression level in chronic phase and the control group. The expression levels of Notch1, Notch2, Jagged1, Hes1 mRNA in blast crisis were higher than those in the control group( P<0.05), but the expression levels of Delta-like1 in chronic phase was lower than that in the control group. The expression levels of Notch1?Notch2 mRNA in blast crisis were higher than those in chronic phase( P<0.05), but the expression levels of Delta-like1 in blast crisis was lower than that in chronic phase. There was no statistically significant difference of Jagged1, Hes1 mRNA expression level in blast crisis and chronic phase. The expression level of Notch1-2, Delta-like1, Jagged1, Hes1 mRNA in chronic phase and blast crisis patients did not related to clinical parameters, such as white blood cell count, hemoglobin, blood platelet count(P>0.05). The correlation expression level of these genes in chronic phase and blast crisis with BCR-ABL/ABL1 was analyzed. The expression level of Delta-like1 mRNA related to BCR-ABL/ABL1 in blast crisis( P<0.05). The Notch1, Notch2, Jagged1 and Hes1 gene may play a role in the pathogenesis of CML,and the Notch1,Notch2 and Delta-like1 gene may promote CML blast crisis. A positive correlation between the Delta-like1 mRNA expression level and BCR-ABL/ABL1 was found in blast crisis, which indicated that Delta-like1 gene may cooperate with BCR-ABL/ABL1 to CML progression.