There is a need to standardize PCR methodology and potential confounding factors need to be addressed before PCR can be generally applied to analysis of minimal residual disease in CML.
We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation.
In patients with chronic myeloid leukemia, the use of real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for measuring BCR-ABL1 transcripts has become standard methodology for the diagnosis and monitoring of minimal residual disease.
The non/late response rate and levels of minimal residual disease in the fusion-positive BCR-ABL1-like group were higher than in the non-BCR-ABL1-like B-others (p<0.01), and also higher, albeit not statistically significant, compared with the fusion-negative BCR-ABL1-like group.
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).
The biological heterogeneity of <i>BCR-ABL1</i>-positive ALL may impact the patient outcomes and optimal treatment (early stem cell transplantation vs long-term administration of tyrosine-kinase inhibitors) as well as on MRD testing.
Real-time quantitative RT-PCR (RT-qPCR, also RQ-PCR) of BCR-ABL1 RNA is a necessary laboratory technique for monitoring the efficacy of tyrosine kinase inhibitor therapy and quantitatively assessing minimal residual disease.
The definition of complete remission in CML may need to be revised in light of the enhanced ability to detect minimal residual disease by PCR technology.
Therefore, quantification of BCR-ABL<sup>I</sup><sup>ns35bp</sup> is useful for evaluating "functional" MRD and determining the effectiveness of TKI with accuracy.
Eight of 9 patients with MRD achieved BCR-ABL1 negativity (complete molecular response, CMR) after a median of one cycle; 2/2 patients without measurable disease durably maintained CMR.
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.
BCR-ABL1 and CRLF2<sup>Re/Hi</sup><sub>,</sub> and that high CD99 mRNA levels are strongly associated with a high frequency of relapse, high proportion of positive for minimal residual disease at day 29 and poor overall survival in paediatric cohorts, which indicate that CD99 is a potential biomarker for BCP-ALL.
A 17-year-old girl with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with persistent minimal residual disease (MRD) who underwent standard chemotherapy was found to have a BCR-ABL1-like gene expression pattern.
A clear correlation was found to exist between the minimal residual disease (MRD) detected in the paired BM and PB samples for all types of leukemias (AML, ALL, and CML), with MRD in PB being approximately one-tenth of that in BM.
Our report suggests a feasible pipeline, in terms of costs and reproducibility, aimed at characterizing and quantifying the genomic BCR-ABL1 rearrangement during MRD monitoring in CML patients.
A new highly sensitive real-time quantitative-PCR method for detection of BCR-ABL1 to monitor minimal residual disease in chronic myeloid leukemia after discontinuation of imatinib.
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.
The exquisite sensitivity of this method, which is capable of detecting as little as a single abnormal molecule of RNA or DNA, makes it suited for the detection of minimal residual disease in both CML and ALL.
Rearrangements of T- and B-cell receptor (TCR and BCR) genes are useful markers for clonality assessment as well as for minimal residual disease (MRD) monitoring during the treatment of haematological malignancies.
Monitoring of minimal residual disease (MRD) by quantification of BCR-ABL1 transcript levels has become a main part of the management of patients with BCR-ABL1-positive acute lymphoblastic leukemia (ALL) in treatment with tyrosine kinase inhibitors (TKIs).
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.
However, BCR-ABL1-independent resistance in the setting of effective BCR-ABL1 inhibition is recognized as a major contributor to minimal residual disease.