The ABL-BCR fusion gene is expressed in chronic myeloid leukemia

Abstract

Although the BCR-ABL hybrid gene on chromosome 22q-plays a pivotal role in the pathogenesis of chronic myeloid leukemia (CML), little is known of the reciprocal chimeric gene, ABL-BCR, formed on chromosome 9q+. By reverse transcription/polymerase chain reaction amplification (RT/PCR) we have detected ABL-BCR mRNA in cells from 31 of 44 BCR-ABL positive CML patients and 3 of 5 CML cell lines. Of the 34 positive samples, 31 had classical t(9;22) (q34;q11) translocations; in 3 samples there was no Philadelphia (Ph) and/or 9q+ chromosomes. ABL-BCR expression consisted of ABL(Ib)-BCR mRNA in 26 patients and of both ABL(Ib)-BCR and ABL(Ia)-BCR mRNA species in 6 patients. The ABL-BCR transcripts encoded one or, more rarely, both of the two potential junctions, designated ABL-b3 and ABL-b4, which differed in size by 75 bp. In 2 patients, the BCR exon b3 was not present in either the BCR-ABL or the corresponding ABL-BCR transcript, whereas in 5 patients exon b3 was present in both transcripts. Direct sequencing of PCR fragments representing the full-length coding sequence of ABL-BCR cDNAs type Ib- b3, Ia-b3, Ib-b4, and Ia-b4 showed an open reading frame predicted to encode fusion proteins of 370 to 414 amino-acids. If an ABL-BCR gene product is produced in CML cells, it may be relevant as a mechanism for deregulating the GTPase activating protein (GAP) function of BCR.

Vaccination with autologous non‐irradiated dendritic cells in patients with bcr/abl+ chronic myeloid leukaemia

“…These data confirm that the fusion region of bcr3/abl2 contains immunogenic T‐cell epitopes, whereas immunogenic peptides from the bcr2/abl2 fusion region have not yet been clearly identified (Bocchia et al , 1995 and 1996). T cells recognizing abl/bcr were reported by Wagner et al (2003), nevertheless, abl/bcr expression at the protein level remains controversial (Melo et al , 1993). T‐cell responses against CML‐associated antigens did not show a clear‐cut TH1/TH2 cytokine pattern, which became particularly apparent in Patient 4 (Table V).…”

True

“…While the bcr-abl gene is expressed in the majority of the chronic myelogenous leukemia patients (CML), the abl-bcr expression can be detected by RT-PCR in only about 59-70%. 1,2 In most of the analyzed cases with rearrangements in the major region of the BCR gene, the junction type in bcr-abl was exactly reciprocal to the junction in bcr-abl, eg a bcr-abl hybrid gene of the type b2-abl correlates with an abl-bcr hybrid gene abl-b3. However, in some cases neither transcripts correlated one with the other.…”

“…These cases included b2-abl patients that expressed only abl-b4 transcripts, thus missing the b3 exon, and b3-abl patients that showed an unexpected abl-b3 hybrid either alone or together with the expected abl-b4 transcript. 1 In the first case, the deletion of the b3 exon could be explained if the deletion took place in the b3 exon itself, or if this exon was included in deletions at the breakpoint site. However, in the second case, only a duplication of the b3 exon could explain this discrepancy.…”

Identification of a novel gene fusion RNF213-SLC26A11 in chronic myeloid leukemia by RNA-Seq

“…Using manual checks and selection, we identified that the majority of fusion events occurred between adjacent genes on the same chromosome, which were usually regarded as read-through (21), while only two candidates, including RNF213-SLC26A11 and BCR-ABL1, were the most reliable gene fusion pairs. BCR-ABL is a well-documented gene fusion in CML and is used as a standard method for CML diagnosis (22). The RNF213-SLC26A11 fusion has not been previously identified in CML.…”