Characterization Of Molecular Biologic Features Of Acute Myeloid Leukemia M2b

Acute Myeloid leukemia (AML) M2b is a new subtype of AML proposed by hematologists of our institute in 1950s basted on the unique morphology of the leukemia cells and the clinical manifestations. Cytogenetic analysis showed that most of the AML—M2b patients had the tC8;21) chromosome abnormalities.AML1 gene and MTG8 gene were recently identified on 21q22 and 8q22 breakpoints, respectively. Thet(8;21) translocation results in the formation of an AML1-MTG8 fusion gene. In order to characterize the molecular biologic features of AML—M2b, the rearrangements of AML1 gene and MTG8 gene and the AML1—TG8 fusion transcript were assayed in 43 cases of AML—M2b and 33 other subtypes of AML. The minimal residual leukemia was monitored in 13 cases of AML —M2b in remission using AML1—MTG8 fusion transcript as a molecular marker. The overall results were as follows:1.Karyotypes were analyzed in 35 cases of AML—M 2b. Four cases (11.4%) had normal diploid karyotypes, while the remaining 31 had t(8;21)(q22;q22). Thirty—hree patients with other subtypes of AML had neither 8q22 nor 21q22 chromosome abnormalities.2. The rearrangement of AML1 gene was assayed in 32 cases of AML—M2b, and was detected in 81.3% of the patients. AMLl gene rearrangement was also detected in 3 of 4 AML—M2b pa-tients with normal diploid karyotype.3. The rearrangement of MTG8 gene was assayed in 30 cases of AML—M2b. MTG8 gene rearrangement was detected in 70.0% of the patients. The MTG8 rearrangement was also detected in 3 of 4 AML—M2b patients with normal diploid karyotype.4. By using reverse transcription polymerase chain reaction (RT—PCR)the transcript of AML1—MTG8 fusion gene was assayed in 40 cases of AML—M2b, the AML1—MTG8 fusion mRNA was detected in all cases studied including 4 cases with normal diploid karyotype and 2 cases who did not show rearrangements of either AMLl gene or MTG8 gene.5. When taking the results of the three assays of AML1 gene rearrangement ,MTG8 gene rearrangement and AML1—MTG8 fusion gene mRNA together, all of the 43 AML—M2b patients studied showed at least one of them positive. On the contrary, in 33 patients with other subtypes of AML only one of the patients assayed showed positive in AMLl gene rearrangement, MTG8 gene rearrangement and AML1—MTG8 fusion gene mRNA, and none of the remaining patients assayed showed positive in any one of these three assays.6. The minimal residual leukemia was monitored by RT —PCR amplification of AML1/MTG8 fusion mRNA. The fusion mRNA were detected in 12 of 13 AML—M2b patients in complete remission(CR), and only 3 of the 12 relapsed. The remaining eight still in their continuous CR (CCR) except one died of myelosuppression during intensification chemotherapy. The only patients who showed the fusion mRNA negative was also in his CCR.