gDNA qPCR is statistically more reliable than mRNA analysis in detecting leukemic cells to monitor CML.

Autor: Rainero A; Department of Medicine and Surgery, University of Insubria, Varese, Italy. alessia.rainero@gmail.com., Angaroni F; Department of Science and High Technology, University of Insubria, Como, Italy.; IFN (National Institute of Nuclear Physics), Como, Italy., D'Avila F; Immunology and Functional Genomics Unit, Centro Cardiologico Monzino IRCCS, via Parea 4, 20138, Milan, Italy., Conti A; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Pirrone C; Department of Biology and Life Sciences, University of Insubria, Varese, Italy., Micheloni G; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Tararà L; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Millefanti G; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Maserati E; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Valli R; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Spinelli O; Department of Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy., Buklijas K; Department of Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy., Michelato A; Department of Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy., Casalone R; Department of Genetics and Cytogenetics, ASST Sette Laghi, Ospedale di Circolo Fondazione Macchi, Varese, Italy., Barlassina C; Department of Health Sciences, University of Milan, Milan, Italy., Barcella M; Department of Health Sciences, University of Milan, Milan, Italy., Sirchia S; Department of Health Sciences, University of Milan, Milan, Italy., Piscitelli E; Biomedical Technologies Institute, CNR, Milan, Italy., Caccia M; Department of Science and High Technology, University of Insubria, Como, Italy., Porta G; Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2018 Mar 02; Vol. 9 (3), pp. 349. Date of Electronic Publication: 2018 Mar 02.
DOI: 10.1038/s41419-018-0387-2
Abstrakt: Chronic Myeloid Leukemia (CML) is a stem cell cancer that arises when t(9;22) translocation occurs in a hematopoietic stem cells. This event results in the expression of the BCR-ABL1 fusion gene, which codes for a constitutively active tyrosine kinase that is responsible for the transformation of a HSC into a CML stem cell, which then gives rise to a clonal myeloproliferative disease. The introduction of Tyrosine Kinase Inhibitors (TKIs) has revolutionized the management of the disease. However, these drugs do not seem to be able to eradicate the malignancy. Indeed, discontinuation trials (STIM; TWISER; DADI) for those patients who achieved a profound molecular response showed 50% relapsing within 12 months. We performed a comparative analysis on 15 CML patients and one B-ALL patient, between the standard quantitative reverse-transcriptase PCR (qRT-PCR) and our genomic DNA patient-specific quantitative PCR assay (gDNA qPCR). Here we demonstrate that gDNA qPCR is better than standard qRT-PCR in disease monitoring after an average follow-up period of 200 days. Specifically, we statistically demonstrated that DNA negativity is more reliable than RNA negativity in indicating when TKIs therapy can be safely stopped.
Databáze: MEDLINE
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