2019年11月13日 · The "gatekeeper" mutation T315I confers resistance against all approved TKIs, with the only exception of Ponatinib, a multi-target kinase inhibitor. CML and Ph+ ALL, rarely present at diagnosis with a BCR/ABL harboring a resistance mutation to TKI.

2020年11月5日 · Asciminib demonstrated clinical activity in heavily pretreated CML pts with or without mutations, with promising efficacy in pts with T315I, including those resistant to/intolerant of (R/I) PON.

BCR-ABL kinase domain mutations are an important cause of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) of which T315I is the most treatment-resilient. This study aimed to observe the frequency of T315I and its impact on disease prognosis in terms of progression and survival.

2014年1月10日 · 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...

2019年12月11日 · Asciminib targets both native and mutated BCR-ABL1, including the gatekeeper T315I mutant. The safety and antileukemic activity of asciminib in patients with Philadelphia chromosome–positive...

We attempted to introduce the T315I gatekeeper mutation into three Ph+ myeloid leukemia cell lines with a seemingly functional HR pathway due to resistance to the inhibitor for poly (ADP) ribose polymerase1.

Use to determine if a variant is present that would interfere with response to TKI therapy in Philadelphia chromosome positive (Ph+) lymphoblastic leukemia or chronic myelogenous leukemia (CML). Detects all common mutations, including T315I.

T315I is a common mutation that accounts for ∼20% clinical resistance to TKIs. We report the first case of a patient with T315I mutated myeloid sarcoma that occurred after complete cytogenetic response with dasatinib of a chronic phase CML.

Of particular concern is the substitution of the threonine residue at the highly conserved gatekeeper residue 315 with a bulkier hydrophobic isoleucine amino acid. This mutation causes steric hindrance precluding the access ATP-competitive inhibitors to the ATP-binding pocket.

The T315I mutation may make cancer cells resistant (unable to respond) to anticancer drugs called tyrosine kinase inhibitors. Checking for the T315I mutation in cancer cells may help plan cancer treatment.