Increasing numbers of patients with chronic myeloid leukaemia (CML) treated with tyrosine kinase inhibitors achieve undetectable levels of BCR-ABL mRNA using sensitive quantitative real-time reverse transcriptase PCR (RT-qPCR) methods and a method to measure minimal residual disease (MRD) in patients with low levels could be of value.
Pre-transplant MRD level of 10 mutant copies of NPM1 per 10,000 Abelson murine leukemia viral oncogene homolog 1 (ABL) copies had the strongest statistical significance, and detection of higher MRD level (>10 NPM1-mutant copies) before alloHSCT was associated with increased overall mortality (hazard ratio=3.71; 95% confidence interval=1.55-9.06; p=0.004).
We simultaneously detected IKZF1 gene deletions by multiplex ligation-dependent probe amplification and gene expression of IKZF1 isoforms in 206 children with BCR/ABL-negative ALL treated with ALL IC-BFM 2002 protocol, in which risk stratification was not based on minimal residual disease (MRD), and validated the results on a cohort of 189 patients treated with MRD-directed ALL-BFM 2000 protocol.
The Abelson (ABL) gene was the best control gene for quantitative PCR (qPCR)-based diagnosis and minimal residual disease detection in leukemic patients.
The combination of IKZF1 deletion and p210 BCR-ABL1 (p < 0.0001), high white blood cell count (p = 0.021), and minimal residual disease (p = 0.013) were associated with worse disease-free survival.
Reverse transcription with random pentadecamer primers improves the detection limit of a quantitative PCR assay for BCR-ABL transcripts in chronic myeloid leukemia: implications for defining sensitivity in minimal residual disease.
This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis.
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.
In chronic myeloid leukemia, the identification of individual BCR-ABL1 fusions is required for the development of personalized medicine approach for minimal residual disease monitoring at the DNA level.
After switching to nilotinib, both BCR-ABL and BCR-ABL<sup>I</sup><sup>ns35bp</sup> became undetectable in 3 patients who attained complete molecular response (CMR), whereas in the remaining all 34 patients, BCR-ABL<sup>I</sup><sup>ns35bp</sup> was persistently detected, and minimal residual disease (MRD) fluctuated at low but detectable levels.
We conclude that BCR/ABL-based MRD monitoring of childhood ALL is a clinically relevant tool and should be performed in parallel with the standard Ig/TCR follow-up.
In patients with chronic myelogenous leukemia (CML) mutations of the BCR-ABL kinase domain (KD) have been identified as the leading cause of acquired resistance to imatinib, while the mechanisms underlying the persistence of minimal residual disease (MRD) are unknown.
A rare e13a3 (b2a3) BCR-ABL1 fusion transcript with normal karyotype in chronic myeloid leukemia: The challenges in diagnosis and monitoring minimal residual disease (MRD).
In search for general PCR targets for minimal residual disease (MRD) studies in acute myeloid leukemia (AML), Wilms' tumor gene 1 (WT1) expression was assessed by real-time RT-PCR relative to the control gene ABL in 569 archived samples of AML patients (pts).
Droplet digital PCR for BCR/ABL(P210) detection of chronic myeloid leukemia: A high sensitive method of the minimal residual disease and disease progression.
The use of a DNA vaccine encoding the BCR/ABL fusion gene is thought to be a promising approach for patients with chronic myeloid leukemia (CML) to eradicate minimal residual disease after treatment with chemotherapy or targeted therapy.
The objective of this prospective, multicentric study was to evaluate MRD by standardized RT-PCR in 178 patients with chronic-phase CML who were treated with imatinib at different institutions in Argentina and Uruguay and to determine if achievement of a stable MMR (BCR-ABL transcript levels < 0.1%) identifies a low-risk cytogenetic relapse group.
We prospectively evaluated minimal residual disease (MRD) by measuring BCR/ ABL levels with a quantitative real-time PCR procedure after induction and after consolidation in 45 adults with Ph+ ALL who obtained complete hematological remission after a high-dose daunorubicin induction schedule.
Thus, dual PP2A and BCR-ABL inhibition may be a valuable therapeutic strategy to synergistically target drug-insensitive LSCs that maintain minimal residual disease in patients.
The observation indicates the need for interrogating rare BCR ABL fusions when common breakpoint cluster regions are absent such that minimal residual disease (MRD), critical for disease monitoring, can be performed and false positive remission cases can be avoided.