Our B-ALL fluorescence in situ hybridization (FISH) panel confirmed the BCR/ABL1 fusion and monosomies consistent with chromosome studies in approximately 95% of interphase nuclei.
FISH signal patterns observed in pediatric ALL cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m-BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies of the Philadelphia chromosome (1.4%).
To our knowledge, the minor BCR-ABL fusion gene involving a secondary Ph superimposed on inv(3) and monosomy 7 has not been reported in AML at diagnosis.
Using a multiparametric cell scanning system that enables combined analysis with probes specific for 7/7q- and BCR/ABL in a single cell, we were able to demonstrate the presence of the BCR/ABL fusion only in cells with monosomy of chromosome 7 and 7q31 deletion, but not in cells with a normal chromosome 7 or with a double deletion of 7q31.
Further molecular and cytogenetic studies confirmed the presence of such typical rearrangements in all except one of these ALL cases who had coexistence of an MBCR/ABL and an mBCR/ABL gene rearrangement together with monosomy 9.
These data support the association of additional Ph and monosomy 7 with poor prognosis and suggest that the novel e2a2 BCR-ABL transcript may be related to an aggressive clinical course.
Examples include the use of allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia with the BCR-ABL fusion gene or MLL rearrangement, and for acute myeloid leukemia with monosomy 7; antimetabolite-based therapy for acute lymphoblastic leukemia cases with hyperdiploidy of more than 50 chromosomes (DNA index > or = 1.16); and retinoic acid and anthracycline-containing regimens for the acute promyelocytic acute myeloid leukemia subtype with PML-RARA fusion.
A combination of monosomy 7 and translocation t(9;22) (q34;q11), rarely observed in acute lymphoblastic leukaemia (ALL), is here reported: a peculiarity of this case was that the "breakpoint cluster region" on chromosome 22 was not rearranged, as demonstrated by molecular analysis, and a new c-abl protein (p190) was found, instead of the usual p210 protein usually associated with the Ph chromosome; moreover a rearrangement of c-abl oncogene was found.