title: A novel BCR-ABL fusion gene (e6a2) in a patient with Philadelphia chromosome-negative chronic myelogenous leukemia.
abstract: A novel variant of the chimeric BCR-ABL mRNA transcript was detected in a patient with Philadelphia chromosome-negative (Ph-) chronic myelogenous leukemia (CML) by multiplex reverse-transcription polymerase chain reaction (RT-PCR). Sequence analysis of the fusion region of the amplified cDNA fragment showed an in-frame joining of exon e6 of the BCR gene and exon a2 of the ABL gene, giving rise to an e6a2 BCR-ABL transcript. This finding was confirmed by Southern blot analysis using a specific probe corresponding to intron 6 of the BCR gene, whereas conventional Southern blot for rearrangement of the major breakpoint cluster region (M-bcr) was negative. Western blot studies detected a BCR-ABL protein slightly larger than p185 BCR-ABL. Metaphase fluorescence in situ hybridization showed an insertion of ABL material into the BCR region without reciprocal BCR translocation. The findings in this case show that atypical BCR-ABL transcripts are detectable even in Ph- CML patients without M-bcr-rearrangements. Multiplex PCR using primers that allow for amplification of all known BCR-ABL transcripts is an appropriate method to exclude these rare variants.
authors.affiliation: III. Medizinische Klinik, Klinikum Mannheim der Universität Heidelberg, Mannheim, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: H
authors.initials: H
authors.lastname: Skladny
authors.forename: J V
authors.initials: JV
authors.lastname: Melo
authors.forename: C
authors.initials: C
authors.lastname: Sick
authors.forename: U
authors.initials: U
authors.lastname: Berger
authors.forename: J Q
authors.initials: JQ
authors.lastname: Guo
authors.forename: R B
authors.initials: RB
authors.lastname: Arlinghaus
authors.forename: R
authors.initials: R
authors.lastname: Hehlmann
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: N C
authors.initials: NC
authors.lastname: Cross
mesh_terms: D000328:Adult; D001483:Base Sequence; D002874:Chromosome Mapping; D017931:DNA Primers / Q000737:chemistry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D016313:Genes, abl; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl