Atypical BCR-ABL mRNA transcripts in adult Acute lymphoblastic leukemia

RT-PCR detects chimeric BCR-ABL mRNA in approximately 25% of adult acute lymphoblastic leukemia (ALL) cases. Minor breakpoint transcripts (e1a2) are found in about 70% of positive cases and major breakpoint transcripts (e13a2, e14a2) in about 30% of cases. However, other atypical transcripts are sometimes observed. We report experience gained in the GMALL Study Group and identified 8 BCR-ABL-positive adult ALL cases with such atypical transcripts: 5 with e1a3, 2 with e13a3 (b2a3), and 1 with e6a2. This corresponds to a prevalence of 1–2% of all BCR-ABL-positive cases. The clinical courses are reported and diagnostic proposals are made.

[1]  P. Jonveaux,et al.  Identification of an Acute Basophilic Leukaemia Carrying a Rare e6a2 BCR-ABL Transcript , 2006, Acta Haematologica.

[2]  Susan O'Brien,et al.  Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. , 2006, The New England journal of medicine.

[3]  M. Mozziconacci,et al.  E6a2 BCR-ABL fusion with BCR exon 5-deleted transcript in a Philadelphia positive CML responsive to Imatinib , 2005, Leukemia & lymphoma.

[4]  P. Paschka,et al.  e8a2 BCR–ABL: more frequent than other atypical BCR–ABL variants? , 2005, Leukemia.

[5]  S. Lee,et al.  Imatinib induces a cytogenetic response in blast crisis or interferon failure chronic myeloid leukemia patients with e19a2 BCR-ABL transcripts , 2004, Leukemia.

[6]  M. Slovak,et al.  Chronic myeloid leukemia with an e13a3 BCR‐ABL fusion: Benign course responsive to imatinib with an RT‐PCR advisory , 2004, American journal of hematology.

[7]  P. Paschka,et al.  Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon α/ara-C , 2003, Leukemia.

[8]  H. Gschaidmeier,et al.  A randomized multicenter open label phase II study to determine the safety and efficacy of induction therapy with imatinib (Glivec, formerly STI571) in comparison with standard induction chemotherapy in elderly (>55 years) patients with Philadelphia chromosome-positive (Ph+/BCR-ABL+) acute lymphobla , 2003, Annals of Hematology.

[9]  D. Niederwieser,et al.  CML with an e1a3 BCR-ABL fusion: rare, benign, and a potential diagnostic pitfall. , 2002, Blood.

[10]  R. Kawaguchi,et al.  Blast crisis of Philadelphia chromosome‐positive chronic myeloid leukaemia carrying micro‐bcr breakpoint (e19a2 and e191a) , 2002, British journal of haematology.

[11]  T. Lipp,et al.  Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. , 2002, Blood.

[12]  J. Reilly,et al.  Are aberrant BCR–ABL transcripts more common than previously thought? , 2000, British journal of haematology.

[13]  G. Saglio,et al.  The e19a2 bcr/abl breakpoint in acute lymphoblastic leukaemia. , 2000, British Journal of Haematology.

[14]  J. Melo,et al.  The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. , 1996, Blood.

[15]  A. Borkhardt,et al.  Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05-92. , 1996, Leukemia.

[16]  E. Thiel,et al.  Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaction , 1991, The Lancet.

[17]  A. Hagemeijer,et al.  A novel variant of the bcr-abl fusion product in Philadelphia chromosome-positive acute lymphoblastic leukemia. , 1990, Leukemia.

[18]  S. Colla,et al.  e6a2 BCR-ABL transcript in chronic myeloid leukemia: is it associated with aggressive disease? , 2004, Haematologica.

[19]  J. Melo,et al.  An optimized multiplex polymerase chain reaction (PCR) for detection of BCR-ABL fusion mRNAs in haematological disorders. , 1994, Leukemia.