A new fused transcript in Philadelphia chromosome positive acute lymphocytic leukaemia

Abstract

The leukaemic cells of more than 90% of chronic myelogenous leukaemia (CML) patients and of 10% of acute lymphocytic leukaemia (ALL) patients carry the t(9:22) (q34:q11) translocation which generates the Philadelphia chromosome (Ph1). In CML the abl gene is translocated from chromosome 9 to the centre of the bcr gene on chromosome 22 and this results in production of chimaeric bcr-abl RNA translated into a protein of relative molecular mass (Mr) 210,000 (210K). Our data indicate that in ALL abl is translocated into the 5' region of the bcr gene. The consequence of this is the expression of a fused transcript in which the first exon of bcr is linked to the second abl exon. This transcript encodes a 190K protein kinase.

JAK-STAT signaling activated by Abl oncogenes

“…Alternatively, the Cterminus of BCR-Abl may not be able to bind JAK kinases. Comparison of Abl protein sequences reveals that although there is a high degree of homology (99%) between murine and human c-Abl in the SH2 and kinase domains (Fainstein et al, 1989), the C-terminus regions (corresponding to the JAK 1-binding domain of v-Abl) are 68% identical. Therefore, it is possible that critical amino acids required for JAK 1 binding within this region are not present in the human protein.…”

Prospective BCR-ABL analysis by polymerase chain reaction (RT-PCR) in adult acute B-lineage lymphoblastic leukemia: reliability of RT-nested-PCR and comparison to cytogenetic data

“…2 The 190 kDa protein results from a break within the minor breakpoint cluster region, splicing the first exon of the bcr gene to the abl gene (e1-a2 junction). 3 Rare fusion transcripts have been identified and are generated for example from a third breakpoint region in the bcr gene ( -bcr) between exon e19 and e20 associated with a p230 protein (c3-a2 junction). 4 The p210 product is the hallmark of chronic myeloid leuke-mia (CML), 5 while p230 seems to be predominantly associated with chronic neutrophilic leukemia.…”

“…1,2 Processing of hybrid transcript results either in an 8.5 kb chimeric messenger RNA (mRNA) that encodes a 210 kDa BCR-ABL protein or in a 7.5 kb mRNA encoding a 190 kDa fusion protein. 2,3 For the p210 protein, exon b2 or b3 of the major breakpoint cluster region is joined to the abl exon 2 (b2-a2 or b3-a2 junction). 2 The 190 kDa protein results from a break within the minor breakpoint cluster region, splicing the first exon of the bcr gene to the abl gene (e1-a2 junction).…”

Molecular and cellular bases of chronic myeloid leukemia

“…The fusion of BCR to ABL during the translocation increases the tyrosine-kinase activity of ABL, and brings new regulatory domains/motifs to ABL, such as the growth factor receptor-binding protein 2 (GRB2) and SH2-binding sites (Li et al, 2001). Depending on the precise breakpoints in the translocation and RNA splicing, different forms of BCR-ABL protein with different molecular weights can be generated in patients, such as P190, P210, and P230 (Groffen et al, 1984;Fainstein et al, 1987;Saglio et al, 1990).…”