Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the translocation leading to the formation of the Philadelphia chromosome, the hallmark of chronic myeloid leukemia (CML), the translocated chromosome 9 (ABL), is of paternal descent whereas chromosome 22 (BCR) is of maternal origin (1). To study possible imprinting of the human ABL and BCR genes, we used human tissues exclusively endowed with their maternally (benign teratoma) or paternally (complete hydatidiform mole) inherited chromosomes. Using the sensitive PCR technique followed by northern blotting, we demonstrate here that ABL and BCR are expressed to a similar extent in androgenetic and gynogenetic human tissues, thus suggesting that ABL and BCR genes are not imprinted in these human tissues.
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PMID:ABL and BCR genes are not imprinted in androgenetic and gynogenetic human tissues. 798 May 23

Induced pluripotent stem cells (iPSCs) can be generated from various differentiated cell types by the expression of a set of defined transcription factors. So far, iPSCs have been generated from primary cells, but it is unclear whether human cancer cell lines can be reprogrammed. Here we describe the generation and characterization of iPSCs derived from human chronic myeloid leukemia cells. We show that, despite the presence of oncogenic mutations, these cells acquired pluripotency by the expression of 4 transcription factors and underwent differentiation into cell types derived of all 3 germ layers during teratoma formation. Interestingly, although the parental cell line was strictly dependent on continuous signaling of the BCR-ABL oncogene, also termed oncogene addiction, reprogrammed cells lost this dependency and became resistant to the BCR-ABL inhibitor imatinib. This finding indicates that the therapeutic agent imatinib targets cells in a specific epigenetic differentiated cell state, and this may contribute to its inability to fully eradicate disease in chronic myeloid leukemia patients.
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PMID:Generation of iPSCs from cultured human malignant cells. 2023 75

Unique biological properties of stem cells make them a precious source of cell material for treatment of a number of pathological conditions. Among issues inhibiting transition of stem cell technologies to the clinics, the risk of oncological complications of stem cell-based therapies is the most critical. A massive amount of clinical and experimental data demonstrates that both hematological (including acute and chronic myeloid leukemia) and non-hematological (including teratoma and non-teratoma tumors) malignancies could arise from donor stem cells of different types. A wide spectrum of mechanisms could underlie the development of oncological disease in recipients, including: i) blast transformation of proliferating donor stem cells under persistent action of certain factors in the recipient, thus causing de novo malignancies; ii) contamination of donor cell material with malignant cells; iii) transmission of particular viral subtypes with donor stem cells, combined with immunosuppression therapy effects; iv) uncontrollable proliferation of residual undifferentiated stem cells of various plasticity; and v) karyotypic instability in stem cells following prolonged culturing/expansion in vitro. Potential preventive strategies are diverse and include i) high-throughput cell sorting-based strategies; ii) introduction of suicide genes into the donor stem cell genome; iii) application of apoptosis-inducing epigenetic factors; and some other options.
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PMID:Risks and mechanisms of oncological disease following stem cell transplantation. 2030 Aug 88

Chronic myeloid leukemia (CML) is a clonal malignancy initiated by the occurrence of a t (9;22) translocation, generating Ph1 chromosome and BCR-ABL oncogene in a primitive hematopoietic stem cell (HSC). The resistance of HSC to targeted therapies using tyrosine kinase inhibitors remains a major obstacle towards the cure. We have generated an iPSC line from a patient with CML using leukemic CD34+ cells cryopreserved at diagnosis. Ph1+ CML cells were reprogrammed by non-integrative viral transduction. These iPSCs harboured Ph1 chromosome and expressed pluripotency hallmarks as well as BCR-ABL. Teratoma assays revealed normal differentiation after injection in immunodeficient mice.
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PMID:Generation of an induced pluripotent stem cell line from a patient with chronic myeloid leukemia (CML) resistant to targeted therapies. 2787 9