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  • inhibit
  • When the levels of these components are thrown off, they can either no longer inhibit apoptosis of the cancer cells, a role fulfilled by BCR/ABL, or they cause apoptosis to be induced, in the same vein as Bax and cytochrome C. These components are key in the mitochondria, and due to this, it has been supported that apoptosis uses the mitochondrial apoptosis pathway. (wikipedia.org)
  • Due to increasing resistance and intolerance to imatinib efforts were made to develop new drugs that could inhibit the Bcr-Abl tyrosine kinase. (wikipedia.org)
  • citation needed] Ponatinib was designed using ARIAD's computational and structure-based drug design platform to inhibit the enzymatic activity of BCR-ABL with very high potency and broad specificity. (wikipedia.org)
  • Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib. (wikipedia.org)
  • selective
  • In the presence of TKI the binding of ATP is blocked, phosphorylation is prevented and Bcr-Abl expressing cells either have a selective growth disadvantage or undergo apoptotic cell death. (wikipedia.org)
  • kinases
  • Different inhibitors have been designed to target different kinases: inhibition of BCR/ABl constitutes the basis of the functioning of drugs like imatinib inhibition of FLT3 is carried out by drugs like lestaurtinib inhibition of JAK2 is carried out by the drug CYT387, which was successful in preclinical trials and is currently undergoing clinical trials. (wikipedia.org)
  • It is a tyrosine kinase inhibitor and works by blocking a number of tyrosine kinases such as Bcr-Abl and the Src kinase family. (wikipedia.org)
  • New forms of resistance can arise as: missense mutations within the Abl kinase domain, over-expression of Bcr-Abl, increased production of transmembrane plasma proteins, or the constitutive activation of downstream signaling molecules such as Src-family kinases. (wikipedia.org)
  • The activity of tyrosine kinases is typically regulated in an auto-inhibitory fashion, but the BCR-Abl fusion gene codes for a protein that is "always on" or continuously activated leading to unregulated cell division (i.e. cancer). (wikipedia.org)
  • Although the BCR region also expresses serine/threonine kinases, the tyrosine kinase function is very relevant for drug therapy. (wikipedia.org)
  • It is an ATP-competitive Bcr-Abl tyrosine-kinase inhibitor with an additional inhibitory effect on SRc family kinases (including Src, Lyn and Hck). (wikipedia.org)
  • Cancer
  • Cyclophosphamide is a prescription medicine used alone, or in combination with other medications to treat several types of cancer including lymphoma, leukemia, ovarian, and breast cancer. (rxwiki.com)
  • Skin cancer and leukemia , which can be fatal, have been reported in patients receiving long-term hydroxyurea for conditions other than sickle cell anemia. (rxwiki.com)
  • Vánky, F. (1976), "Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia", International Journal of Cancer, 18 (4): 421-31, doi:10.1002/ijc.2910180405, PMID 789258 Andersson, L.C. (wikipedia.org)
  • Chronic myelogenous leukemia (CML) is a cancer of the white blood cells. (wikipedia.org)
  • Even though the first Bcr-Abl TK inhibitor was named "the magic bullet" to cure cancer by TIME magazine, a second generation of Bcr-Abl TKI was subsequently developed to combat the initial resistance that emerged. (wikipedia.org)
  • As Musashi2 is involved in the generation of hematopoietic cells, it is also linked with cancer pathologies: It has been found that MSI2 plays an important role in myeloid leukemia. (wikipedia.org)
  • kinase domain
  • Since then crystallographic studies have revealed that imatinib binds to the kinase domain of Abl only when the domain adopts the inactive or "closed" conformation. (wikipedia.org)
  • This is due to the replacement of the myristoylated cap region, which when present induces a conformational change rendering the kinase domain inactive, with a truncated portion of the BCR protein. (wikipedia.org)
  • fusion
  • The cells are non-adherent and rounded, are positive for the bcr:abl fusion gene, and bear some proteomic resemblance to both undifferentiated granulocytes and erythrocytes. (wikipedia.org)
  • Since ABL activates a number of cell cycle-controlling proteins and enzymes, the result of the BCR-Abl fusion is to speed up cell division. (wikipedia.org)
  • adherence
  • However, another study suggests that bcr:abl over-expression may actually increase cell adherence to cell culture plastic. (wikipedia.org)
  • mortality
  • the occurrence of acute and chronic graft versus host disease, survival, transplantation-related mortality, and relapse rates were compared. (clinicaltrials.gov)
  • phosphorylation
  • In the presence of TKI the binding of ATP is blocked, phosphorylation is prevented and Bcr-Abl expressing cells either have a selective growth disadvantage or undergo apoptotic cell death. (wikipedia.org)
  • activates
  • Since ABL activates a number of cell cycle-controlling proteins and enzymes, the result of the BCR-Abl fusion is to speed up cell division. (wikipedia.org)
  • Nilotinib
  • The importance of early and deeper molecular responses on the risk of progression and blast crisis has been proven in the DASISION and ENESTnd trials leading to the approval of both dasatinib and nilotinib as first line TKIs along with imatinib in both the National Comprehensive Cancer Network (NCCN) and European Leukemia Net (ELN) guidelines. (rbhh.org)
  • Tumors
  • In children, acute lymphoblastic leukemia and brain tumors are most common, except in Africa where non-Hodgkin lymphoma occurs more often. (tfode.com)
  • On 1 February 2012, imatinib was approved for use after the surgical removal of KIT-positive tumors to help prevent recurrence. (wikipedia.org)
  • bone marrow
  • Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). (yale.edu)
  • also called acute lymphocytic leukemia) is a cancer of the blood and bone marrow . (yale.edu)
  • Also, as the number of leukemia cells increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. (yale.edu)
  • A chronic disease of the blood and bone marrow that results from a transformation of a stem cell. (cmladvocates.net)
  • It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. (wikipedia.org)
  • Blast crisis is diagnosed if any of the following are present in a patient with CML: >20% myeloblasts or lymphoblasts in the blood or bone marrow Large clusters of blasts in the bone marrow on biopsy Development of a chloroma (solid focus of leukemia outside the bone marrow) The only curative treatment for CML is a bone marrow transplant or an allogeneic stem cell transplant. (wikipedia.org)
  • Bosutinib
  • The positive opinion for bosutinib was based on data from Study 200, a global, single-arm, open-label, multi-cohort, Phase 1/2 study of bosutinib in more than 500 patients with Ph+ CML with separate cohorts for chronic, accelerated and blast phase disease previously treated with one or more prior TKIs. (biospace.com)
  • We are very pleased with this positive recommendation on bosutinib by the CHMP. (biospace.com)
  • subsequently
  • The patient was subsequently tested by RQ-PCR for BCR-ABL on a six-monthly basis [November 2012 (0.00%), March 2013 (0.069%), October 2013 (0.062%), January 2014 (0.008%), September 2014 (0.0024%), December 2015 (0.00%), and June 2016 (0.00%)] ( Figure 1 ). (rbhh.org)
  • Progression
  • Blast crisis is the final phase in the evolution of CML, and behaves like an acute leukemia, with rapid progression and short survival. (wikipedia.org)
  • Patients
  • Importantly, the panel of lines displayed the critical genetic features identified in clinically important acute lymphoblastic leukemia subtypes in childhood leukemia patients. (aacrjournals.org)
  • It also describes the current risk stratification models and discusses the vascular and hemorrhagic risks that affect patients with this chronic condition, including younger individuals and pregnant women. (hematologyandoncology.net)
  • Due to the high median age of patients with CML it is relatively rare for CML to be seen in pregnant women, despite this, however, chronic myelogenous leukemia can be treated with relative safety at any time during pregnancy with Interferon-alpha hormones. (wikipedia.org)