DETECTION OF THE CHROMOSOME-16 CBF-BETA-MYH11 FUSION TRANSCRIPT IN MYELOMONOCYTIC LEUKEMIAS

Karyotypic detection of chromosomal 16 abnormalities classically assoc iated with AML M4Eo can be difficult. Characterization of the two gene s involved in the inv(16)(p13q22), CBF beta and MYH11, has allowed the detection of fusion transcripts by reverse-transcriptase polymerase c hain reaction (RT-PCR). We have analyzed CBF beta-MYH11 fusion transcr ipts by RT-PCR in myelomonocytic leukemias, with or without eosinophil ia, to determine whether their presence correlates with morphology. Fi fty-three cases (11 AML M4Eo; 1 AML M4 with atypical abnormal eosinoph ils (AML M4 ''Eo''); 29 AML M4; 8 AML M5; 3 CMML; and 1 AML M2 with eo sinophilia) were analyzed. All 11 typical AML M4Eo were CBF beta-MYH11 positive. The single case of AML M4 with distinctive eosinophil abnor malities was negative by karyotype, RT-PCR and fluorescent in situ hyb ridization (FISH). Three of 29 (10%) AML M4 without abnormal eosinophi ls were CBF beta-MYH11 positive, 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis (2 not tes ted). Both cases tested also showed MYH11 genomic rearrangement. None of the other leukemias were RT-PCR positive. Follow-up of three patien ts showed residual positivity in apparent complete remission. These da ta show that CBF beta-MYH11 fusion transcripts occur not only in the v ast majority of typical AML M4Eo, but also in approximate to 10% of AM L M4 without eosinophilic abnormalities, a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would su ggest. Taken together with the detection of CBF beta-MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical b anding techniques, these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4, regardless of morph ologic features, to allow accurate evaluation of the prognostic import ance of this fusion transcript. (C) 1995 by The American Society of He matology.