<p>Monitoring of Minimal Residual Disease (MRD) in Chronic Myeloid Leukemia: Recent Advances</p>

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the BCR-ABL1 fusion gene generation as a consequence of the t(9;22)(q34;q11) rearrangement. The identification of the BCR-ABL1 transcript was of critical importance for both CML diagnosis and minimal residual disease (MRD) monitoring. In this review, we report the recent advances in the CML MRD monitoring based on RNA, DNA and protein analysis. The detection of the BCR-ABL1 transcript by the quantitative reverse-transcriptase polymerase chain reaction is the gold standard method, but other systems based on digital PCR or on GeneXpert technology have been developed. In the last years, DNA-based assays showed high sensitivity and specificity, and flow cytometric approaches for the detection of the BCR-ABL1 fusion protein have also been tested. Recently, new MRD monitoring systems based on the detection of molecular markers other than the BCR-ABL1 fusion were proposed. These approaches, such as the identification of CD26+ leukemic stem cells, microRNAs and mitochondrial DNA mutations, just remain preliminary and need to be implemented. In the precision medicine era, the constant improvement of the CML MRD monitoring practice could allow clinicians to choose the best therapeutic algorithm and a more accurate selection of CML patients eligible for the tyrosine kinase inhibitors discontinuation.

Molecular Testing in CML between Old and New Methods: Are We at a Turning Point?

“…In the last few years, many studies have been conducted in order to overcome the intrinsic limitations of "classical" quantitative PCR (RT-qPCR) [8,9] (such as the limit of detection fixed at three copies of BCR-ABL1 transcript, the need for a standard curve, or the sensitivity to inhibitors), both improving its performance [10,11] and looking at further novel technologies [12]. In this context, digital PCR (dPCR) seems to be one of the most promising tools [13,14].…”

Understanding and Monitoring Chronic Myeloid Leukemia Blast Crisis: How to Better Manage Patients

“…BCR-ABL monitoring should be performed monthly for the first 6 to 12 months during TKI discontinuation and may be tapered off after that to avoid recurrence. 4 , 6 , 69 , 71–77…”

“…The disease is caused by the BCR-ABL fusion gene generated from the t (9;22)(q34;q11) reciprocal translocation, encoding the BCR-ABL oncoprotein, which constitutively activates ABL kinase and drives hematopoietic cell proliferation and leukemic transformation. [1][2][3][4][5][6] CML is a natural triphasic course disease starting with the indolent CP, which is characterized by a remarkable increase in myeloid precursors and mature cells and lasts approximately 3-5 years. 7 Without therapeutic intervention, after a median interval of 3-18 months, the disease spontaneously progresses to AP and eventually to highly aggressive BP, characterized by a rapid expansion of primitive cells in the bone marrow that spill into circulation, 8,9 similar to acute leukemia.…”

The Combination of Interferon-Alpha and Ponatinib Enables Faster and Deeper Molecular Responses in Patient with De Novo Blast Crisis of CML: Interferon-Alpha May Return as a CML Treatment

“…For patients with chronic phase CML (CML-CP) who cannot obtain optimal response, some investigators were using a combination of IFN- α and TKI for treatment [ 5 , 6 ]. Through this combination treatment, they have succeeded in obtaining a durable DMR [ 7 ]. In this report, we present a case of a patient with de novo blast crisis treated with the same combination after the chemotherapy to obtain early DMR and maintain a stable condition.…”