E6a2BCR-ABLfusion withBCRexon 5-deleted transcript in a Philadelphia positive CML responsive to Imatinib

Abstract

Chronic myeloid leukemia (CML) is characterized in 90% of patients by the presence of the reciprocal translocation t(9;22)(q34;q11) leading to the fusion of the BCR and ABL genes. Most patients with Philadelphia chromosome positive CML express either the e13a2 (b2a2) or e14a2 (b3a2) MBCR-ABL mRNA. Some variant cases have been reported expressing the fusion e1a2 (mBCR-ABL) or e19a2 (microBCR-ABL). Very rare atypical transcripts such as e13a3, e14a3 or e6a2 have been described. We report here a sixth case of a Ph positive patient with an e6a2 BCR-ABL fusion transcript and describe for the first time a chimeric molecule alternatively spliced for exon 5 of the BCR gene.

Chronic myeloid leukemia (CML) with P190BCR-ABL: analysis of characteristics, outcomes, and prognostic significance

“…1 Rarely, the minor breakpoint cluster region (m-bcr) may be involved with a resultant fusion transcript e1a2. [2][3][4][5] Other transcripts such as e19a2, 2,6,7 e2a2, 8 e1a3, e6a2, e13a3(b2a3), and e14a3(b3a3) 9,10 occur less frequently. The e13a2(b2a2)/e14a2(b3a2) fusion transcripts encode for a 210-kDa protein (P210 BCR-ABL ), whereas the e1a2 encodes for a 190-kDa protein (P190 BCR-ABL ), and the e19a2 encodes for a 230-kDa protein (P230 BCR-ABL ).…”

Atypical BCR-ABL mRNA transcripts in adult Acute lymphoblastic leukemia

“…17 The transcript levels in affected patients are very low, and the transforming capacity of the resulting p230 chimeric bcr-abl protein appears to be relatively weak. Most CML cases with atypical BCR-ABL transcripts reported in the literature had a more benign course and were responsive to imatinib and/or interferon α, 9,11,18,19 but myeloid blast crises have also occasionally been noted. 18,20 Theoretically, all atypical BCR-ABL transcripts should in principle be responsive to imatinib treatment, regardless of whether BCR sequences are fused to ABL exon 2 or 3, since they all encode the ATPbinding pocket (i.e.…”

Complete molecular response of e6a2 BCR-ABL–positive acute myeloid leukemia to imatinib then dasatinib

“…Further variant BCR-ABL rearrangements affecting other regions of the BCR gene have also been described. [1][2][3][4][5][6][7][8][9][10][11][12] A very rare fusion transcript joining the first 6 exons of BCR to exon 2 of ABL (e6a2) has been reported in 4 cases of CML with an aggressive clinical course. [2][3][4][5] More recently, this translocation has been reported in single cases of chronic myelomonocytic leukemia, 13 T-cell acute lymphoblastic leukemia, 14 and acute basophilic leukemia.…”