A Novel BCR-ABL Fusion Gene (e6a2) in a Patient With Philadelphia Chromosome-Negative Chronic Myelogenous Leukemia

• Published in: Blood Vol. 88; no. 6; pp. 2236 - 2240
• Main Authors: Hochhaus, A., Reiter, A., Skladny, H., Melo, J.V., Sick, C., Berger, U., Guo, J.Q., Arlinghaus, R.B., Hehlmann, R., Goldman, J.M., Cross, N.C.P.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.09.1996; The Americain Society of Hematology
• Subjects: Adult; Base Sequence; Biological and medical sciences; Chromosome Mapping; DNA Primers - chemistry; Fusion Proteins, bcr-abl - genetics; Genes, abl; Hematology; Humans; In Situ Hybridization, Fluorescence; Investigative techniques, diagnostic techniques (general aspects); Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - genetics; Male; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; RNA, Messenger - genetics; RNA, Neoplasm - genetics; Translocation, Genetic; Human; Reverse transcription; Exploration; Malignant hemopathy; Polymerase chain reaction; Myeloproliferative syndrome; Chronic; Messenger RNA; C-Onc gene; Chronic myelocytic leukemia; Atypical; Technique; Molecular biology; Hybrid gene; Protooncogene
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V88.6.2236.bloodjournal8862236

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. Meta-phase 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.