The BCL2 inhibitor ABT-199 significantly enhances imatinib-induced cell death in chronic myeloid leukemia progenitors
Tun Kiat Ko1, Charles T.H. Chuah1,2, John W.J. Huang1 , King-Pan Ng1 and S. Tiong Ong
Tun Kiat Ko1, Charles T.H. Chuah1,2, John W.J. Huang1 , King-Pan Ng1 and S. Tiong Ong
This article is a retrospective, single-institution review of the incidence and clinical characteristics of late chronic anemia associated with prolonged use of imatinib for patients with chronic myeloid leukemia. The authors reported a 30% incidence of late chronic anemia associated with a prolonged use of imatinib, with no effect on overall survival.
24/10/2014
European Medicines Agency recommends further measures to minimise risk of blood vessel blockage with Iclusig
The European Medicines Agency (EMA) has concluded its review of the benefits and risks of Iclusig (ponatinib), a medicine used for the treatment of leukaemia (cancer of the white blood cells), and has recommended strengthened warnings in the product information aimed at minimising the risk of blood clots and blockages in the arteries.
Treatment Recommendations for People Living with CML
This is a summary of the European public assessment report (EPAR) for Imatinib Teva. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of
Timothy Hughes and Deborah White.
10 Mar 2014
Researchers in Manchester have investigated the stickiness of leukaemia cells, and whether this is linked to drug resistance.
News | September 03, 2014 | Leukemia & Lymphoma, Chronic Myeloid Leukemia, Hematologic Malignancies
By Dave Levitan
STAT3 inhibition using a novel compound restored sensitivity to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cells that had shown resistance independent of BCR-ABL1 kinase activity, according to a new study published in the journal Leukemia. The findings could help fill gaps in CML treatment for patients with unexplained resistance to TKIs.
L Schafranek1,2,3, E Nievergall1,2,3, J A Powell4,5, D K Hiwase3,6, T Leclercq1,3, T P Hughes1,2,3,6,7 and D L White1,2,3,4
Kinase inhibitors block proliferative signals in BCR-ABL1+ leukemic cells, but their capacity to induce apoptosis is poorly understood. Initial studies suggested that very brief exposure to kinase inhibitors was sufficient to induce apoptosis in chronic myeloid leukemia (CML) cells. However, flaws in this experimental model have subsequently been identified, leading to the conclusion that apoptosis only occurs with sustained low-level kinase inhibition. Thus, the minimum duration of complete kinase inhibition required to commit CML cells to death is unknown. Here we confirm that <1 h is insufficient to induce significant commitment to death in BCR-ABL1+ cell lines and in primary CD34+ progenitor cells, and establish that commitment to cell death only occurs if kinase inhibition is maintained for 4 h or more. Remarkably, signal transducer and activator of transcription 5 (STAT5) inhibition in combination with transient (<1 h) tyrosine kinase inhibitor (TKI) exposure proved lethal for CML progenitors, despite the reactivation of Bcr-Abl after 1 h. JAK kinase inhibition did not induce cell death in combination with transient TKI exposure. Thus, STAT5 appears to be a critical determinant of the time-dependent sensitivity of CML progenitor cells to TKI treatment in a Bcr-Abl-dependent, but JAK-independent, manner. We conclude that combining kinase inhibition with STAT5 inhibition represents a promising therapeutic approach in BCR-ABL1+ leukemias.
Wesam Ahmed and Richard A. Van Etten