Is Wilms’ tumor gene 1 a useful biomarker for detecting minimal residual disease in chronic myeloid leukemia (BCR-ABL1-p210-positive) patients?

Abstract Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by the presence of Philadelphia (Ph) chromosome. Wilms’ tumor gene 1 (WT1) plays an important role in leukemogenesis and can be useful as a molecular marker to detect minimal residual disease (MRD). The goal of this study was to evaluate WT1 expression and compare it with BCR-ABL1 expression in peripheral blood (PB) of CML patients, in order to explore the utility of WT1 as an alternative marker for MRD detection. Eighteen newly diagnosed CML patients (BCR-ABL1-p210-positive), 16 chronic CML patients with a history of imatinib therapy, and 18 normal individuals (BCR-ABL1-p210-negative) as controls were enrolled in this study. WT1 and BCR-ABL1 expression was evaluated by quantitative real-time polymerase chain reaction (Q-RT-PCR). Analysis of RT-PCR data was performed using REST Software (2009, QIAGEN, Valencia, USA). Data were analyzed by SPSS software (v.16.0) using Spearman’s rho and Kruskal-Wallis methods. WT1 expression in all PB samples of newly diagnosed CML patients was significantly higher than that of the normal individuals (P = 0.003). WT1 expression was not different in patients on imatinib therapy compared to normal individuals (P = 0.6), but it was significantly lower than that of the newly diagnosed CML patients (P = 0.001). There was no significant correlation between expression of WT1 and BCR-ABL1 and...
Source: Comparative Clinical Pathology - Category: Pathology Source Type: research

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Conditions:   Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive;   Acute Lymphoblastic Leukemia in Remission;   Acute Myeloid Leukemia in Remission;   Chronic Lymphocytic Leukemia;   Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive;   Cytomegalovirus Positive;   H ematopoietic Cell Transplant Recipient;   Hodgkin Lymphoma;   Lymphadenopathy;   Lymphoblastic Lymphoma;   Myelodysplastic Syndrome;   Myelofibrosis;   Myeloproliferative Neoplasm; ...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 10 August 2019Source: Seminars in Cancer BiologyAuthor(s): Peter Valent, Irina Sadovnik, Gregor Eisenwort, Harald Herrmann, Karin Bauer, Niklas Mueller, Wolfgang R. Sperr, Daniel Wicklein, Udo SchumacherAbstractThe development of a myeloid neoplasm is a step-wise process that originates from leukemic stem cells (LSC) and includes pre-leukemic stages, overt leukemia and a drug-resistant terminal phase. Organ-invasion may occur in any stage, but is usually associated with advanced disease and a poor prognosis. Sometimes, extra-medullary organ invasion shows a metastasis-like or even sarcoma...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Chronic myeloid leukemia (CML) is caused by the fusion of the BCR activator of RhoGEF and GTPase activating protein (BCR) and ABL proto-oncogene, the nonreceptor tyrosine kinase (ABL) genes. Although the tyrosine kinase inhibitors (TKIs) imatinib (IM) and nilotinib (NI) have remarkable efficacy in managing CML, the malignancies in some patients become TKI-resistant. Here, we isolated bone marrow (BM)-derived mesenchymal stem cells (MSCs) from several CML patients by Ficoll-Hypaque density-gradient centrifugation for coculture with K562 and BV173 cells with or without TKIs. We used real-time quantitative PCR to assess the l...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
ConclusionWe identified key candidate targets and pathways for CML LSCs through bioinformatics methods, which improves our understanding of the molecular mechanisms of CML LSCs. These candidate genes and pathways may be therapeutic targets for CML LSCs.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
We reported previously that combined BCR-ABL1 and BCL-2 inhibition synergistically targets chronic myeloid leukemia stem/progenitor cells. p53 induces apoptosis mainly by modulating BCL-2 family proteins. Although infrequently mutated in chronic myeloid leukemia, p53 is antagonized by MDM2, which is regulated by BCR-ABL1 signaling. We hypothesized that MDM2 inhibition could sensitize chronic myeloid leukemia cells to tyrosine kinase inhibitors. Using an inducible transgenic Scl-tTa-BCR-ABL1 murine chronic myeloid leukemia model, we found, by RT-PCR and CyTOF proteomics increased p53 signaling in chronic myeloid leukemia bo...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Leprosy drug clofazimine activates peroxisome proliferator-activated receptor-γ and synergizes with imatinib to inhibit chronic myeloid leukemia cells. Haematologica. 2019 Aug 01;: Authors: Kumar H, Chattopadhyay S, Das N, Shree S, Patel D, Mohapatra J, Gurjar A, Kushwaha S, Singh AK, Dubey S, Lata K, Kushwaha R, Mohammed R, Ghosh Dastidar K, Yadav N, Vishwakarma AL, Gayen JR, Bandyopadhyay S, Chatterjee A, Jain MR, Tripathi AK, Trivedi AK, Chattopadhyay N, Ramachandran R, Sanyal S Abstract Leukemia stem cells contribute to drug-resistance and relapse in chronic myeloid leukemia and BCR-ABL1 inh...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
In conclusion, TARP qualifies as a relevant target for immunotherapeutic T-cell therapy in acute myeloid leukemia. PMID: 31371409 [PubMed - as supplied by publisher]
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
oslash;rgensen HG Abstract Tyrosine kinase inhibitor (TKI) therapy is the standard treatment for chronic phase (CP)-chronic myeloid leukemia (CML), yet patients in blast crisis (BC) phase of CML are unlikely to respond to TKI therapy. The transcription factor E2F1 is a down-stream target of the tyrosine kinase BCR-ABL1 and is up-regulated in TKI-resistant leukemia stem cells (LSC). Pyrrole imidazole polyamides (PA) are minor groove binders which can be programmed to target DNA sequences in a gene-selective manner. This manuscript describes such an approach with a PA designed to down-regulate E2F1 controlled gene e...
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Tags: Bioorg Med Chem Lett Source Type: research
Authors: Shan Y, DeSouza N, Qiu Q, Li S Abstract Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the BCR-ABL oncogene encoding a constitutively activated tyrosine kinase. Although BCR-ABL tyrosine kinase inhibitors (TKIs) are highly effective in treating CML at chronic phase, a number of patients develop drug resistance due to the inability of TKIs to kill leukemia stem cells (LSCs). Similar to other types of hematopoietic malignancies, LSCs in CML are believed to be a rare cell population responsible for leukemia initiation, disease ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Xie X, Feng M, Wang Q, Wang J, Yin R, Li Y, Zhang H Abstract Leukemia stem cells (LSCs) are leukemia-initiating population with the capacity to self-renew, differentiate, and stay quiescent. Human hematopoietic malignancies such as chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) are derived from this cell population. LSCs are also responsible for disease relapse due to its resistance to drug treatment. This rare cell population is phenotypically and functionally heterogeneous. Increasing evidence indicates that this heterogeneous cellular state of LSCs might determine the different dru...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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