Identification of an Acute Basophilic Leukaemia Carrying a Rare e6a2 BCR-ABL Transcript

ripheral blood analysis showed moderate anaemia (Hb 10 g/dl), thrombocytopenia (platelet count 51 ! 10 9 /l) and hyperleucocytosis (WBC 80.8 ! 10 9 /l), which included 8% myeloid cells and 30% blasts. Of these, 24% had coarse basophilic granules and 6% were undifferentiated blasts. There were 8% basophilic precursors and 5% mature basophils. Bone marrow aspirate revealed a cellular marrow with 33% blasts including 28% with coarse basophilic granules and 5% undifferentiated blasts associated with 12% basophilic precursors and 4% mature basophils ( fig. 1 a). Auer rods were not seen. The blasts were negative for myeloperoxidaxe and nonspecific esterase. Basophilic granules in the blasts and basophils exhibited metachromasia with toluidine blue. Immunophenotyping with four-colour flow cytometry was performed on bone marrow. Blasts were gated on their dim CD45 and low sidescatter characteristics. They expressed a myeloid phenotype since they were positive for CD13, CD33, CD11c and CD203c, a specific basophilic marker. Blasts were negative for early haematopoietic markers (CD34, HLA-DR, TdT), for B and T lymphoid markers (CD10, CD19, CD20, CD22, CD2, CD3, CD5) and for other myeloid markers (CD14, CD15, CD65, CD117, MPO). Cytogenetic analysis, performed on 24and 48-hour bone marrow cultures, The t(9; 22)(q34;q11) translocation has been implicated as the causative factor in greater than 95% of chronic myelogenous leukaemia (CML), in 25–30% of adult and 2–10% of childhood acute lymphoblastic leukaemia (ALL) and in rare acute myelogenous leukaemia (AML). This translocation generates a fusion gene between the 5 part of the BCR gene and the 3 part of the c-ABL gene. In CML, the breakpoint in BCR usually falls in the major breakpoint cluster region (M-bcr) with junctions e13a2, e14a2 and less frequently e13a3, e14a3, as in two thirds of ALL. In rare cases of CML and other ALL cases, it is located in minor breakpoint (m-bcr) with junctions e1a2 and rarely e1a3. More recently, a third bcr region called micro-bcr was detected with juxtaposition of exon 19 to ABL (e19a2) [1] . In this report we describe a new case of BCR-ABL fusion with chromosome 22 breakpoint unusually located in BCR intron 6 resulting in e6a2 junction. Only six cases have been reported to our knowledge [2–7] , and it is the first one associated with acute basophilic leukaemia features. A 71-year-old male was referred to our care unit because of a bilateral pneumopathy. On clinical examination, there was no hepatosplenomegaly or cutaneous lesions or symptoms related to hyperhistaminaemia. PeReceived: February 8, 2006 Accepted after revision: February 14, 2006