Acute myeloblastic leukaemias of FAB types M6 and M4, with cryptic PML/RARalpha fusion gene formation, relapsing as acute promyelocytic leukaemia M3

Demonstration of either the translocation t(15;17)(q22;q21) or the fusion o f PML and RAR alpha genes is regarded as diagnostic for acute myeloid leuka emia (AML) of FAB type M3, but has occasionally been seen in other FAB type s. We present two such cases. Case 1 presented with FAB type M6 and a compl ex karyotype involving chromosomes 1, 2, 11 and 17. Bone marrow relapse of FAB type M3 followed autologous bone marrow transplantation. Subsequent mar row dysplasia and an M6 relapse were accompanied by a new cytogenetic clone involving chromosomes X, 2, 4, 6, 7 and 16. Fluorescence in situ hybridiza tion (FISH) of metaphase chromosomes at diagnosis showed insertion of mater ial from chromosome 17 into a 'normal' 15 with juxtaposition of PML and RAR alpha. Case 2 presented as AML M4 and relapsed as M3. Cytogenetic analysis at diagnosis and in relapse showed 46,XY,t(15;17)(q22;q11),del(16)(q22). F ISH analysis showed this to be a three-way translocation. involving chromos omes 15, 16 and 17 again with juxtaposition of PML and RARa. Reverse transc ription-polymerase chain reaction (RT-PCR) revealed PML/RAR alpha fusion at diagnosis, in remission and in first relapse. These examples strengthen th e case for RT-PCR screening of all AML patients for these fusion genes.