Triple Philadelphia chromosomes with major-bcr rearrangement in hypotriploid erythroleukaemia

The Philadelphia (Ph) chromosome is observed in approximately 1% of patient s with acute myeloblastic leukaemia (AML), especially subtypes M1 and M2 in the French-American-British classification. We describe here a cytogenetic and molecular investigation of a rare case with Ph-positive AML M6 (erythr oleukaemia). A 63-yr-old woman was diagnosed as having erythroleukaemia. Le ukaemic cells were positive for CD4 and CD7 as well as CD13, CD33, CD34 and HLA-DR. They were analyzed by G-banding, fluorescence in situ hybridizatio n (FISH), Southern blot and reverse transcriptase polymerase chain reaction analyses. The karyotypes at diagnosis were as follows. 61, XX. - X, - 1, - 2, -3, -4, -5, -7, t(9;22)(q34;q11) x 2, -15, -16. -17, -18, +19, +21, +22 [3]/61, idem, -22, +der(22)t(9;22) [36]. FISH with BCR/ABL probes showed th at 39% and 57% of interphase nuclei had double and triple BCR/ABL fusion si gnals, respectively. Chromosome analysis in complete remission showed a nor mal karyotype in all 20 metaphases, confirming the diagnosis as Ph positive -acute leukaemia. FISH at relapse showed that 92% of interphase nuclei had triple fusion signals. Rearrangement of major breakpoint cluster region (M- bcr) in the BCR gene and coexpression of p210-type (b2a2) and p190-type (e1 a2) BCR/ABL fusion transcripts due to alternative splicing were also detect ed. We conclude that clonal evolution from double to triple Ph chromosomes may be implicated in the disease progression. Considering other two reporte d cases, Ph-positive erythroleukaemia appears to be correlated with coexpre ssion of myeloid/T-lymphoid markers and hyperdiploidy with double or triple Ph chromosomes. although breakpoints in the BCR gene are heterogenous.