| Objective: To investigate the cytogenetics of leukemia and its clinical therapeutic significance. Methods: Karyotypes from a total of 169 de novo leukemia cases were centrally reviewed. Specimens were obtained at diagnosis from spina iliaca posterior superior of all patients. Chromosomal analyses of bone marrow(BM) were performed in cytogenetics laboratories. Specimens were processed using direct methods, unstimulated short-term(24-,and 48-hour) cultures, or both. G-banding was performed. The criteria to describe a cytogenetic clone and description of karyotype followed the recommendations of the International System for Human Cytogenetic Nomenclature. At least 20 BM metaphase cells were analyzed in patients designated as having a normal karyotype. All the patients were classified to acute myelogenous leukemia (AML), acute lyphoblastic leukemia (ALL) and chronic myelocytic leukemia (CML) groups according to different FAB (French-American -Britian) types of leukemia. AML group were classified to acute promyelocytic leukemia ( APL or M3 ) and non-APL subgroups. ALL group were classified to normal karyotype and abnormal karyotype subgroups. CML group were classified to chronic phase(CP), accelerated phase(AP) and blastic phase(BP) subgroups. Results: 1. Among all of the 169 leukemia cases ,96 were male, 73 were female, the age were from 6 to 80, the median age was 36. Of these cases 103 were AML,23 were ALL,38 were CML, one were chronic lyphoblastic leukemia(CLL)with normal karyotype , one were chronic neutrophilic leukemia(CNL)with normal karyotype ,three were acute mixed-cytoblastic leukemia who did not reach remission. Among the last three cases one had Philadelphia (Ph) chromosome,one had Ph chromosome accompanied with 5q+, the other one was complicated karyotype. 2. The incidence of cytogenetic abnormalities of APL cases was the highest among AML while that of erythroleukemia (EL or M6) was the lowest, which were 63.3%and 25.0%, respectively. The total incidence of cytogenetic abnormalities of AML was 50.5%. The t(15;17) aberration was the most frequently presented one in AML, which had 15 cases in all, and only presented in APL. There were 12 cases of t(8;21),8 of AML with maturation (M2), 1 of acute myelomonocytic leukemia ( AMML or M4 ), 2 of AML with eosinophilia (M4EO),and 1 of acute monocytic leukemia (AMoL or M5).14 out of 15 t(15;17) achieved remission ,the remission rate was 93.3%.9 out of 12 t(8;21) achieved remission, the remission rate is 75.0%. There were 25 cases of other cytogenetic abnormalities, the remission rate was 52.0%. There were statistical significance among the outcome of the three groups, P<0.05.There was statistical significance between the t(15;17) group and the other cytogenetic abnormalities group, P<0.017. There was no statistical significance between the t(15;17) group and the t(8;21) group, P>0.05. And there was no statistical significance between the t(8;21) group and the other cytogenetic abnormalities group, P>0.05. 3. +8 chromosome abnormality was presented in M2,M3,M4,M5 and M6 subtypes. The total remission rate was 50%. 4. The outcome of a M4EO case with inv(16) chromosome abnormality was non-remission(NR). The outcome of a M4 case with t(9;22)chromosome abnormality was part-remission(PR). 5. There were 51 AML cases with normal karyotype. Fourteen of them were NR, the remainder were CR or PR. The remission rate was 72.5%. 6.Among 12 cases with t(15;17) chromosome abnormality,7(58.3%) were WT1 negative, the remission rate was 100%,5(41.7%) were WT1 positive, the remission rate was 75%. Among 6 cases with t(8;21) chromosome abnormality, 4(66.7%) were WT1 negative, the remission rate was 100%, 2(23.3%) were WT1 positive, the remission rate was 50%. 7.The incidence of cytogenetic abnormalities of ALL was 47.8%, t(9;22) is the highest one. The remission rate between cases with normal and abnormal karyotype were different, which were 91.7% and 45.5%,respectively (P<0.05). Four cases of t(9;22) chromosome abnormality were adults, and the outcome of one case was complete remission (CR), the other three were NR. The remission rate of cases with t(9;22) chromosome abnormality was 25.0%. Among the four cases two had double Philadelphia (Ph) chromosome and were NR. The outcome of one case was NR even after peripheral blood stem cell transplantation (PBSCT). 8. The incidence of cytogenetic abnormalities in CML was 97.4%. There were 34 cases(89.5 % ) having typical Ph translocation t(9;22)(q34;q11) and 2 cases(5.3%) having atypical Ph translocation. These data indicated that there were specific cytogenetic factors in the pathogenesis of CML. 9. There were 30 CML-CP cases whose rate of CML was 78.9%. One was t(5;9;22)(q31;q34;q11) whose outcome was PR. One was normal karyotype whose outcome was PR. 9 of 28 t(9;22) cases reached hematopoietic complete remission(HCR) and the other 19 cases reached PR. Of the 19 PR cases 3 had additional cytogenetic aberrations. There were 2 CML-AP cases both were t(9;22)(q34;q11) whose rate of CML was5.3%. The outcome of one case was NR, and developed into BP a month later. The outcome of another one was PR. 10. There were 6 CML-BP cases whose rate of CML was 15.8%. Four developed into AML whose rate was 10.5%. Two developed into ALL whose rate was 5.3%. Two CML-BP cases had atypical Ph transplantation, they did not reached hematopoietic complete remission(HCR) after a month of the therapy of imatinib mesylate (STI571). Conclusions: 1. AML,ALL,CLL all have their pathogenetic base of cytogenetic abnormalities. Cytogenetics is an important therapeutic and prognostic factor to leukemia. 2. There are differences among the outcomes of different FAB subtypes of AML, M3 being the highest, M1,M2,M4,M5 intermediate,M6 the lowest. 3. T(15;17)(q22;q21) is a favorable prognostic factor and only presented in APL. Additional cytogenetic disorder such as +8, 8p-and 20p+ do not influence its optimistic prognosis. 4. T(8;21)(q22;q22) usually presents in M2 with a favorable prognosis,and sometimes in M4 and M5 with an intermediate prognosis. 5. +8 chromosome abnormality can be seen in M2,M3,M4,M5,M6 with an intermediate prognosis. 6. Inv(16)(p13;q22) is an unfavorable prognostic factor when accompanied with advanced age, higher white blood cell count (WBC) and lower platelet count. 7. The outcome of AML cases with normal karyotype are intermediate. 8. There is no correlation between WT1 gene and the karyotypic pattern of AML cases. As to t(15;17) and t(8;21) chromosome abnormalities, the remission rate of cases with WT1(-) is higher than cases with WT1(+).9. The remission rate of abnormal karyotype cases is worse than normal ones in ALL. The t(9;22) aberration presents most frequently among the former group with a poor prognosis. The outcome of double Ph chromosome cases is unfavorable. 10. The typical Ph translocation is the hallmark of CML. Additional chromosomal abnormalities in BP result in unfavorable prognosis. 11. The outcome of cases having atypical Ph transplantation in CML-BP is unfavorable even after the therapy of imatinib mesylate. |
