Expression And Significance Of TGF-β₁,TGF-β Type II Receptor And C-myc In Patients With Leukemia

Objiective: Leukemia is the most common type of all hematopoietic tumors. The prominent character of leukemia is malignant proliferation, obstruction of differentiation and apoptosis of primitive and premature cells . The proliferation , differentiation, maturation and apoptosis of hematopoietic cells are regulated by a complex cytokine net which are composed of stimulating cytokines and inhibiting cytokines .Under biological circumstance , positive and negtive rugulation signals are well balanced, so the hematopoietic homeostasis are maintained .Among the negative factors, transforming growth factor beta (TGF-β) is the most potent being studied most thoroughly.TGF- β belongs to a family of dimeric polypeptide growth factors . The three allotypes of TGF- β (TGF- β_1,2,3 ) has been discovered in human cells, and the distibution of them are tissue-specific. Practically, normal cell and transformed cell can produce TGF-β and its cognate receptors. TGF-β is involved in the proliferation and differentiation of cells, embryonic development, secretion of extracellular matrix,angiogenesis and immuneregulation. In particular, TGF-P can signal cell cycle arrest and is a potent inhibitior to the proliferation of epithelial cells, endothelia cells and hematopoietic cells , which has made it a research focus on tumors .It is known that hematopoietic cells produce TGF-P ,, a most potent inhibitor to hematopoietic cell proliferation. Autocrined and paracrined TGF-3, by hematopoietic stem cell and bone marrow stromal cell plays an important role in keeping the stem cell and progenitor cell quiescent and inhibiting their over-proliferation .In addition , TGF-P can inhibit leukemic cell proliferation and induce its apoptosis.The development of tumors are related to abnormal TGF-P signaling . It has been reported in documents of foreign languages that hematopoietic malignant tumors such as leukemia and lymphoma have abnormal TGF-3 signaling . In our country research about TGF-P signal were focused on solid tumor, and similar studies in leukemia were few. So in this study , immunocytochemical staining was applied to detect the expression of ligand(TGF^P ,) , type II receptor(TP RII), and a target gene (OMyc) of TGF- P signaling pathway .The purpose is to explore the relationship between abnormal TGF- P signal and leukemogenesis , and provide theoretical and experimental basis for leukemia therapy with TGF-P signal regulator.Mater i a Is and method:(1) subjects were divided into three groups: ? the acute lymphocytic leukemia(ALL) group (n=19, male 14, female 5, median age 33Y) (2) the acute myeloid leukemia (AML) group ( N=33, male 20, female 13, median age 37Y ) ?the control group (N=12, male 4, female 8, median age 29.5Y) (2) the mononuclear cells of all subjects were seperated from the bone marrow and the expression of TGF-P M TPRII and C-Myc in each group were detected by S-P immunocytochemical staining (3) all patients with acute leukemia was divided into two groups according-to median of OMyc expression (groupH: C-Myc expression ^median) (group L: C-Myc expression 0. 05).2. The positive expression ratio of TPRII in group AML, ALL and control was (31.56 ± 14.85)% , (32.43 ± 22.28)% , (69.07 + 24.56)% respectively. The score of T3RII in AML, ALL and control was 51.88 + 26. 32, 49.89 + 30.62, 113. 50±47. 98 respectively. The expression of TPRII in AML and ALL were both lower than that in control (p<0. 05). There was no significant difference of TPRII expression between AML and ALL (p>0. 05).3. The positive expression ratio of C-Myc in group AML, ALL and control was (75.15 + 22.45)% , (67.67 + 31.29)% , (31.08 + 24.67)% respectively. The score of C-Myc in AML, ALL and control was 129.81+ 71.66, 119.71±75.53, 39. 50+37. 19 respectively. The expression of C-Myc was higher in AML and ALL than that in control (p<0.05). There was no significant difference of C-Myc expression between AML and ALL (p>0.05).4. The peripheral blood WBC count, Hb concentration , Pit count and percentage of leukemic cells in bone marrow smear in group H was(67.64 + 86.17) X109/L, (75. 96±22. 75)g/L, (35. 31+24. 92) X 109/L and(71±17)% respectively ; and the number in group L was (63. 63 + 95. 63)X 107L , (76.27 + 22. 56) g/L , (45. 77±57.45) X 109/L and (67+22) %respectively. There was no significant difference of WBC count , Hb concentration , Pit count and percentage of leukemic cells between group H and group L (p>0.05).5. C-Myc expression was negtively related to TPRII expression(r=-0. 538, p<0. 01).No relation was discovered between TGF-P , and TPRII expression , so do TGF-P , and C-Myc .Con I us ions:1. There was no significant difference of TGF-P , expression among AML ■. ALL and control (p>0. 05). It is supposed that acute leukemic cell can produce at least the same amount TGF-P ,.2. The expression of TPRII in AML and ALL were much lower than that in control (p<0. 05). It is supposed that the down-regulation of TPRII was involved in leukemogenesis.3. The expression of C-Myc in AML and ALL were much higher than that in control(p<0. 05). In addition , C-Myc expression was negatively related to TPRII expression. Both co-operate to make the leukemic cell escape TGF-Pi inhibitory effect .