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.
Four patients presented with B-lymphoblastic leukemia (B-ALL), and of them, two patients with t(8;9)(p22;p24.1) were proven to be B-lymphoblastic crisis of MPN; and the other two cases with t(9p24;v) both were de novo B-ALL, BCR-ABL1-like (Ph-like).
Inducible genetic attenuation of BCR-ABL reversed Bmi1-driven B-ALL development, which was accompanied by induction of apoptosis of leukemic B-lymphoid progenitors and by long-term animal survival, suggesting that BCR-ABL is required to maintain B-ALL and that BCR-ABL and Bmi1 cooperate toward blast transformation in vivo.
RCSD1-ABL1-positive B lymphoblastic leukemia is sensitive to dexamethasone and tyrosine kinase inhibitors and rapidly evolves clonally by chromosomal translocations.
Recurrent genetic abnormalities in B-lymphoblastic leukemia with prognostic significance are well known and specifically delineated in the WHO 2008 classification (eg hyperdiploidy, t(9;22)(q34;q11.2); BCR-ABL1, t(12;21)(p13;q22); ETV6-RUNX1).
Notably, genetic alteration of the lymphoid transcription factor gene IKZF1 is a hallmark of multiple subtypes of ALL with poor prognosis, including BCR-ABL1-positive lymphoid leukemia and a subset of 'BCR-ABL1-like' ALL cases that, in addition to IKZF1 alteration, harbor genetic mutations resulting in aberrant lymphoid cytokine receptor signaling, including activating mutations of Janus kinases and rearrangement of cytokine receptor-like factor 2 (CRLF2).
Since BACH2 induces apoptosis by oxidative stress, these observations suggest that down-regulation of the BACH2 gene through the interaction with centromeric heterochromatin would take part in leukomogenesis of BCR-ABL positive lymphoid leukemia.
Using a murine model of chronic myeloid leukemia, an adult-onset malignancy that arises from transformation of hematopoietic stem cells by the BCR-ABL(P210) oncogene, we demonstrate that young bone marrow (BM) cells that were transformed with BCR-ABL(P210) initiated both a myeloproliferative disorder (MPD) and B-lymphoid leukemia, whereas BCR-ABL(P210)-transformed old BM cells recapitulated the human disease by inducing an MPD with rare lymphoid involvement.
In contrast, recent observations in human BCR-ABL1(+) pre-B lymphoblastic leukemia cells demonstrate that Btk is constitutively phosphorylated and activated by the BCR-ABL1 fusion protein.
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.
The human BCR-ABL oncogenes encoded by the Philadelphia chromosome (Ph) affect the pathogenesis of diverse types of leukemia and yet are rarely associated with T-lymphoid leukemia.