The past decade has witnessed tremendous progress in the treatment of acute lymphoblastic leukaemia (ALL), primarily due to the development of targeted therapies, including tyrosine kinase inhibitors targeting BCR-ABL1 tyrosine kinase, monoclonal antibodies targeting cell surface antigens (CD19, CD20 and CD22), bispecific antibodies and chimeric antigen receptor T- cell therapy.
There have been successful examples of targeted therapy improving the outcome of some childhood cancers, such as the addition of an ABL class tyrosine kinase inhibitor to conventional chemotherapy substantially improving the cure rate for patients with BCR-ABL1 positive acute lymphoblastic leukemia.
There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia.
Molecular detection of the <i>BCR-ABL1</i> fusion transcripts is necessary for the genetic confirmation of a chronic myeloid leukemia diagnosis and for the risk classification of acute lymphoblastic leukemia.
At the 60<sup>th</sup> month, estimated CBMR and CEMR incidences were, respectively, 14.3 (5.1)% and 25.9 (6.6)% in ALL, 25.8 (5.9)% and 15.5 (4.8)% in AML, and 61.5 (16.5)% and 17.9 (13.4)% in CML.
At current work, the combination of sensors were used to detect the presence of BCR-ABL1 as a mutant gene and CEA as a biomarkers of cancer, such a capability makes the package liable for early and certain detection of acute lymphoblastic leukemia.
BCR-ABL1 signal patterns were analyzed using FISH in 243 CML-chronic phase (CML-CP), 17 CML-blast phase (CML-BP) and 52 BCR-ABL1 positive acute lymphoblastic leukemia (ALL) patients.
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).
An 11-year-old male patient with the deletion of <i>IKZF1</i> (Ikaros family zinc finger 1) and positive Breakpoint Cluster Region-C-Abelson oncogene 1(<i>BCR-ABL1</i>) acute lymphoblastic leukemia developed mucositis, gastrointestinal toxicity, hepatotoxicity, myelosuppression, and severe dermatologic toxicity during the first and second courses of high-dose methotrexate.
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.
This case illustrates the major interest of interphase FISH for BCR-ABL1 rearrangement on blood neutrophils as a decisive method to discriminate a lymphoid blast crisis of CML from a de novo BCR-ABL1 positive ALL.
BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements.
HDAC1,2 inhibition and doxorubicin impair Mre11-dependent DNA repair and DISC to override BCR-ABL1-driven DSB repair in Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia.
CD25 (IL-2RA) and CD26 (DPPIV) were expressed on LSCs in Ph<sup>+</sup> ALL exhibiting BCR/ABL1<sub>p210</sub>, whereas in Ph<sup>+</sup> ALL with BCR/ABL1<sub>p190</sub>, LSCs variably expressed CD25 but did not express CD26.
<i>IKZF1</i> gene defects are associated with inferior treatment outcome in both childhood and adult B-cell precursor acute lymphoblastic leukemia and occur in more than 70% of <i>BCR-ABL1</i>-positive and <i>BCR-ABL1</i>-like cases of acute lymphoblastic leukemia.
Phosphatase of regenerating liver-3 <i>(PRL-3/PTP4A3)</i> is upregulated in multiple cancers, including BCR-ABL1- and ETV6-RUNX-positive acute lymphoblastic leukemia (ALL).
To address this, we studied 142 adults with ALL treated with hyperCVAD over a 10-year period who had MRD assessed by either multi-parameter flow cytometry or (for patients with Philadelphia chromosome positive ALL) reverse transcriptase polymerase chain reaction for the BCR-ABL1 translocation.
The breakpoint cluster region-ABL proto-oncogene 1 (<i>BCR-ABL</i>) rearrangement leads to a p210 chimeric protein in typical chronic myeloid leukemia (CML), whereas 17-25% of patients with acute lymphocytic leukemia and 0.9-3% patients with <i>de novo</i> acute myeloid leukemia (AML) carry a p190<sup>BCR-ABL</sup> fusion protein.