title: Acute myeloblastic leukaemias of FAB types M6 and M4, with cryptic PML/RARalpha fusion gene formation, relapsing as acute promyelocytic leukaemia M3.
abstract: Demonstration of either the translocation t(15;17)(q22;q21) or the fusion of PML and RARalpha genes is regarded as diagnostic for acute myeloid leukaemia (AML) of FAB type M3, but has occasionally been seen in other FAB types. We present two such cases. Case 1 presented with FAB type M6 and a complex karyotype involving chromosomes 1, 2, 11 and 17. Bone marrow relapse of FAB type M3 followed autologous bone marrow transplantation. Subsequent marrow dysplasia and an M6 relapse were accompanied by a new cytogenetic clone involving chromosomes X, 2, 4, 6, 7 and 16. Fluorescence in situ hybridization (FISH) of metaphase chromosomes at diagnosis showed insertion of material from chromosome 17 into a 'normal' 15 with juxtaposition of PML and RARalpha. 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). FISH analysis showed this to be a three-way translocation involving chromosomes 15, 16 and 17 again with juxtaposition of PML and RARalpha. Reverse transcription-polymerase chain reaction (RT-PCR) revealed PML/RARalpha fusion at diagnosis, in remission and in first relapse. These examples strengthen the case for RT-PCR screening of all AML patients for these fusion genes.
authors.affiliation: Department of Haematology, The Royal Free and University College School of Medicine, Royal Free Campus, University College London, UK. andres@talk21.com
authors.forename: A
authors.initials: A
authors.lastname: Virchis
authors.forename: E
authors.initials: E
authors.lastname: Massey
authors.forename: T
authors.initials: T
authors.lastname: Butler
authors.forename: P
authors.initials: P
authors.lastname: Devaraj
authors.forename: F
authors.initials: F
authors.lastname: Wright
authors.forename: L
authors.initials: L
authors.lastname: Secker-Walker
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
authors.forename: A
authors.initials: A
authors.lastname: Mehta
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000628:therapy; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012008:Recurrence; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D014182:Transplantation, Autologous; D025521:Tumor Suppressor Proteins
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human