These findings suggest that MSCs may be in part tumor-related, highlighting an unrecognized role of the BM milieu on the pathogenesis of MLL-AF4(+) B-ALL.
Since γ-catenin was dispensable for normal hematopoiesis, these lineage- and disease-specific features of canonical Wnt signaling identified a potential therapeutic target for the treatment of BCR-ABL1<sup>+</sup> B-ALL.
The paired box domain of PAX5 was reported to fuse with the sequence of promyelocytic leukemia (PML) to produce PAX5-PML chimeric protein in two patients with B-cell acute lymphoblastic leukemia.
Regulated Pax5-Etv6 target genes identified in these B-ALLs encode proteins implicated in pre-B-cell receptor (BCR) signaling and migration/adhesion, which could contribute to the proliferation, survival, and tissue infiltration of leukemic B cells.
The TEL-AML1 transgenic zebrafish models human pre-B ALL, identifies the molecular pathways associated with leukemia development, and serves as the foundation for subsequent genetic screens to identify modifiers and leukemia therapeutic targets.
The degree of anemia was significantly different for three distinct groups of patients compared to the remaining patients (mean hemoglobin; T-cell leukemia: 106 g/L versus 76 g/L (precursor B-cell acute lymphoblastic leukemia); within precursor B-cell ALL: TEL-AML1 positive: 68 g/L versus 79 g/L; BCR-ABL positive: 93 g/L versus 76 g/L; each p<0.05).
The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC).
Screening for ABL1 chimeric genes could be performed in patients with ALL, more particularly in those with T-cell ALL because ABL1 modulates T-cell development and plays a role in cytoskeletal remodeling processes in T cells.
A 74-year-old man was previously diagnosed with BCR-ABL1-positive pre-B cell acute lymphoblastic leukaemia (pre-B ALL) based on bone marrow cytology, flow cytometry, cytogenetics and fluorescent in situ hybridisation findings.
To gain insight into the genomic landscape of infant MLL-AF4 pro-B ALL we performed whole genome sequencing of diagnostic leukemic blasts and matched germline samples from three MLL-AF4 pro-B ALL infants.
We show that the B cell blockage at the pro-B to pre-B cell transition is due to a large homologous deletion in the IGH locus encompassing the IGHM gene leading to the inability to form a functional pre-BCR.
However, it is unknown whether PTEN functions as a tumor suppressor in human Philadelphia chromosome-positive leukemia that includes chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL) and is induced by the BCR-ABL oncogene.