Cytogenetic Changes Of Multiple Myeloma And Its Clinical Significance

OBJECTIVE: Evaluation of the effect of modified cell culture on detection of abnormal karyotype in MM patients. Retrospective analysis of the deletion chromosome 13 in MM patients at diagnosis were performed with FISH technique. Clinical significance of FISH-defined partial deletion chromosome 13 in MM patients were investigated.METHODS: RHG banding was used to study the common cytogenetic changes and to evaluate the effect of culture method modification(long term culture and addition of growth factors) on abnormal karyotype detection in 20 MM patients. Archival bone marrow smears from 68 MM patients at diagnosis were used to study and compare the deletion of Rb~l gene and locus 13ql4. 3 by FISH analysis. Chi-square test was used to study the relations between partial deletion of chromosome 13 and clinical featuress; Log-rank test, Cox' s regression and Kaplan-Meier method were used in survival analysis. RESULTS: 16 cases analyzed by RHG-banding were evaluable, culture method had effect on the cytogenetic detection : abnormal karyotype were detected in 4 cases after 6 days culture with addi tion of IL-6 and GM-CSF; 3 cases with complex karyotype, 1 case with del(13ql4) only; these were proved by FISH using probes specific for Rb-1 gene. 35 out of 68(51%) cases were found with partial deletion of chromosome 13, 29 cases (43%) with deletion of Rb-1 gene; 23 out of 44 cases (52%) with deletion of 13ql4. 3; 66%(29/44) cases with the same result in above analysis. Chi-square test showed partial deletion of chromosome 13 was associated with serum creatine levels, detection of plasmablastic eel 1s, hemoglobin levels, numbers of bone lensions,early chemotherapy responses, 1 year survival; LDH levels, detection of plasmablastic cells and type of light chains were found associated with prognosis in Log-rank Lest; detection of plasmablastic cells and serum creatine levels were found to be significant single prognostic factors ; no prognostic implications were found for partial deletion of chromosome 13.CONCLUSIONS: Longer culture period with addition of IL-6 and GM-CSF improves the cytogenetic analysis of MM patients, complex karyotype arecommon changes in MM. Applicat ion of FISH on archival bone marrow smears is a simple, liable method, can be readly used to retrospective study of clonal hematopoieitc system diseases. Deletion of Rb~l gene and locus 13q 14.3 were common changes in MM, abnormalities of chromosome 13 may be larger deletion involving both Rb-1 and 13ql4.3 in some patients. Partial deletion of chromosome 13 affect the biological behavior of MM cases; detection of plasmablastic cells and serum creatine level were significantly and independly prognostic factors for MM patients, no prognostic implications were found for partial deletion of chromosome 13 due to the sample size.