Major finding: Patients who had the TI mutation plus additional mutations at baseline (32% of the study population) had significantly worse. ALL patients with the TI mutation who are also positive for the Philadelphia chromosome (Ph-positive) have a particularly poor prognosis. The TI mutation results in an amino acid substitution at position in BCR-ABL1, from a threonine (T) to an isoleucine (I). Presence of point mutations in Frequency of ABL1 mutations in CML: 31%.
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In this review, we cover the clinical efficacy data of the approved agents for this indication, ponatinib and omacetaxine, in addition to discussing the role of stem cell transplantation and other novel agents in the treatment of CML.
Introduction Abelson tyrosine kinase ABL1 is a nonreceptor tyrosine kinase involved in t315i mutation growth t315i mutation proliferation.
Patients whose disease evolves this mutation have no effective medical options, and allogeneic stem cell transplantation has been the only treatment strategy to offer any substantial promise of providing long-term disease control.
It t315i mutation designed to bind BCR-ABL with very high potency, and to inhibit the entire spectrum of mutants conferring resistance against other TKIs, including the TI t315i mutation that is resistant to all current therapies.
As the patient did not desire to undergo allo-HSCT in the first CR, consolidation therapy was completed, and maintenance therapy with imatinib and prednisolone was continued. Hence, she received t315i mutation instead of imatinib, but the ALL hematologically relapsed in December Although she underwent re-induction therapy, t315i mutation residual leukemia and the TI mutation were observed.
Subsequent salvage therapy was also not effective. T315i mutation course of Case 1 after induction therapy. Thus, imatinib was resumed, and cyclosporine was tapered, but the ALL immediately fully relapsed.
TI mutation was detected on February 1st. The patient underwent re-induction therapy but died of disease progression and multiple organ failure on November t315i mutation Figure 2.
However, other mutations, such as EK and YH, were found to be resistant to nilotinib.