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.
In the COALL cohort, these patients had unfavourable outcome (5-year disease-free survival 59.5%, 95% CI 37.1-81.9) compared with patients with other precursor B-ALL (84.4%, 76.8-92.1%; p=0.012), a prognosis similar to that of patients with BCR-ABL1-positive ALL (51.9%, 23.1-80.6%).
A total of 14 lymphocytic leukemia patients were examined, seven with acute lymphocytic leukemia (ALL), two with adult T-cell leukemia (ATL), two with B-chronic lymphocytic leukemia (CLL), two with chronic myelocytic leukemia in lymphoid blastic crisis (CML-LBC), and one with plasma cell leukemia (PCL).
To characterize the subset of ALL with normal karyotype or failed CBA, we performed fluorescence in situ hybridization (FISH) or PCR for BCR-ABL1 and MLL rearrangements as well as array comparative genomic hybridization (aCGH) in 186 adult patients.
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.
We demonstrated the dPCR is high-sensitive (able to detect a single copy of BCR-ABL1) and reliable (results are comparable to those obtained by BCR-ABL1 quantification with conventional technology), allowing an accurate monitoring of BCR-ABL1-positive ALL patients in complete remission.
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.
Thirty-one patients (27 with acute myeloid leukemia [AML], 2 with acute lymphocytic leukemia [ALL], and 2 with acute mixed lineage leukemia [AMLL]) treated with conventional chemotherapy (CHT) and 23 patients (13 AML, 5 ALL, and 5 with chronic myeloid leukemia [CML]) treated with allogeneic bone marrow transplantation (BMT) were monitored for WT1 expression levels in BM and peripheral blood (PB) by reverse transcriptase-polymerase chain reaction over a long-term period (mean, 29 months for CHT and 24 months for BMT).
These include new subtypes of acute myeloid leukemia defined by mutations in <i>RUNX1</i> or <i>BCR-ABL1</i> translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia.
We have mapped breakpoints within the 8.3-kb BamHI breakpoint cluster region in 31 patients with acute lymphoblastic leukemia and acute myeloid leukemia (AML) de novo and in 8 t-AML patients.
Rearrangements in the BCR gene first intron, the so-called bcr2 and bcr3 regions, were detected in two other cases, one with an acute lymphoblastic leukemia (ALL) and one with mixed acute leukemia.
The prognostic value of IKZF1 deletions was evaluated in 2 cohorts of BCR-ABL1-positive BCP-ALL patients, before tyrosine kinase inhibitors (pre-TKI) and after introduction of imatinib (in the European Study for Philadelphia-Acute Lymphoblastic Leukemia [EsPhALL]).
The abnormalities with the most significant impact for treatment and management of BCP-ALL are t(9;22)(q34;q11)/BCR-ABL1, t(4;11)(q21;q23)/MLL-AFF1 and near-haploidy/low hypodiploidy for high risk stratification and, to a lesser extent, t(12;21)(p13;q22)/ETV6-RUNX1 and high hyperdiploidy for good risk management.
Cellular localization of beta-catenin protein was detected by immunocytochemistry. beta-Catenin gene expression was significantly increased in AML compared with ALL cases (P < 0.0001), Ph+ CML (P < 0.0001) and non-neoplastic haematopoiesis (P = 0.019).
To identify oncogenic lesions that combine with BCR-ABL1 to cause ALL, we used Affymetrix Genome-Wide Human SNP arrays (250K NspI and SNP 6.0), fluorescence in situ hybridization, and genomic polymerase chain reaction to study 106 cases of adult BCR-ABL1-positive ALL.
We report here observations on the occurrence of intermediate pre-B/B-cell phenotypes, immunoglobulin isotype switching and the asynchrony of immunoglobulin heavy and light chain expression in 30 cases of ALL and 3 cases of chronic myelogenous leukaemia in lymphoblastic crisis (CML-BC).
One recently identified subtype of pediatric B-precursor acute lymphoblastic leukemia (ALL) has been termed BCR-ABL1-like or Ph-like because of similarity of the gene expression profile to BCR-ABL1 positive ALL suggesting the presence of lesions activating tyrosine kinases, frequent alteration of IKZF1, and poor outcome.