Variant · Snv

ABL1 T315I

CI-VAR-00004310Explore in graph →NP_005148.2:p.Thr315IleNM_007313.2:c.1001C>TClinVar 12624 CIViC 2 rs121913459

Curated evidence

Evidence by cancer (54 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–50 of 54 evidence items across 3 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Acute Lymphoblastic Leukemia8
BCR::ABL1 Fusion AND ABL1 T315I	Axitinib + PonatinibSubstitutes	Predictive	D	Does Not Support Resistance	3	accepted	EID7777 Bone marrow mononuclear cells (BM MNCs) were isolated from three acute lymphoblastic leukemia patients with the BCR-ABL1 T315I variant who were pretreated with various chemotherapeutics and dasatinib.… (full text at CIViC) PMID 25686603 · Pemovska et al., 2015 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Predictive	C	Supports Resistance	2	submitted	EID4374 In a retrospective study of 45 imatinib-resistant or -intolerant Philadelphia chromosome BCR-ABL fusion positive (Ph+) chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia (ALL) patients, pati… (full text at CIViC) PMID 17339191 · Soverini et al., 2007 ·

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
12624	Likely pathogenic; association	criteria provided, multiple submitters, no conflicts	2	Leukemia, Philadelphia chromosome-positive, resistant to imatinib; Chronic myeloid leukemia	germline/somatic	3	Sep 13, 2023	clinvar

Chronic Myeloid Leukemia, BCR-ABL1 Positive41
ABL1 T315I	Asciminib	Predictive	A	Supports Sensitivity Response	4	submitted	EID11225 In phase 1, dose-escalation trial 141 patients with chronic-phase chronic myeloid leukemia (CML) and 9 patients with accelerated-phase CML who had previously taken at least two ATP-competitive tyrosin… (full text at CIViC) PMID 31826340 · Hughes et al., 2019 · Open in CIViC	civic
ABL1 T315I	Dasatinib	Predictive	D	Supports Resistance	2	rejected	EID6284 In an in vitro study, stochastic mutations were introduced into the ABL1 region of a stably expressed p210 BCR-ABL fusion in Ba/F3 cells using N-ethyl-N-nitrosourea mutagenesis. Resulting clones were … (full text at CIViC) PMID 16772610 · Bradeen et al., 2006 · Open in CIViC	civic
ABL1 T315I	Nilotinib	Predictive	D	Supports Resistance	3	rejected	EID6195 In an in vitro study, stochastic mutations were introduced into the ABL1 region of a stably expressed p210 BCR-ABL fusion in Ba/F3 cells using N-ethyl-N-nitrosourea mutagenesis. Resulting clones were … (full text at CIViC) PMID 16772610 · Bradeen et al., 2006 · Open in CIViC	civic
ABL1 T315I	Ponatinib	Predictive	A	Supports Sensitivity Response	4	submitted	EID11226 In a phase 2, dose-reduction trial, 282 patients were enrolled who had previously been treated with at least 2 prior TKIs or had a T315I mutation. Efficacy was assessed on an interim analysis based on… (full text at CIViC) PMID 34407543 · Cortes et al., 2021 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	(prognostic)	Prognostic	B	Supports Better Outcome	4	submitted	EID8044 T315I is an unfavorable mutation in the BCR-ABL1translocation leading to Chronic Myeloid Leukemia. In this article, experts review and compile the literature regarding the use of Ponatinib (a tyrosine… (full text at CIViC) PMID 31590170 · Saussele et al., 2020 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Axitinib	Predictive	C	Supports Sensitivity Response	4	accepted	EID4369 In this study, enzymatic profiling, crystal structures, and proliferation assays using Ba/F3 with the BCR-ABL1 variant showed higher sensitivity to axitinib in fusions with the T315I variant of ABL1 c… (full text at CIViC) PMID 25686603 · Pemovska et al., 2015 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Axitinib	Predictive	D	Supports Sensitivity Response	2	submitted	EID4370 In an in vitro study, primary tumor cells from 2 chronic myeloid leukemia patients (endogenous) and pro-B Ba/F3 cells (overexpression) harboring T315I mutation in the ABL1 portion of the BCR-ABL1 fusi… (full text at CIViC) PMID 26239229 · Okabe et al., 2015 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Axitinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID4371 In an in vitro study, pro-B Ba/F3 cell line expressing T315I mutation in the ABL1 portion of the BCR-ABL1 fusion protein (overexpression) demonstrated increased sensitivity to axitinib treatment (IC50… (full text at CIViC) PMID 26582647 · Zabriskie et al., 2016 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Axitinib	Predictive	D	Supports Sensitivity Response	3	submitted	EID4372 In an in vitro study, a KBM-5 cell line expressing T315I mutation in the ABL1 portion of the BCR-ABL fusion protein (overexpression) demonstrated sensitivity to axitinib treatment, comparable to KBM-5… (full text at CIViC) PMID 26912052 · Halbach et al., 2016 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Bosutinib	Predictive	C	Supports Resistance	2	accepted	EID4362 This was a retrospective study of dasatinib and/or nilotinib-resistant or -intolerant patients pretreated with imatinib aimed at evaluating the efficacy of bosutanib monotherapy. All patients had chro… (full text at CIViC) PMID 22371878 · Khoury et al., 2012 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Bosutinib	Predictive	C	Supports Resistance	2	accepted	EID4364 In this retrospective study, imatinib-resistant or -intolerant patients, with chronic phase CML and BCR-ABL fusions, were treated with bosutanib monotherapy. Complete hematologic response (CHR) and ma… (full text at CIViC) PMID 21865346 · Cortes et al., 2011 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Bosutinib	Predictive	D	Supports Resistance	2	submitted	EID4361 In an in vitro study, a Ba/F3 murine cell line stably expressing the T315I mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with reduced sensitivity to bosutinib treatment (I… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Predictive	B	Supports Resistance	3	accepted	EID4365 This is a retrospective study of imatinib-resistant (n = 805) or -intolerant (n = 238), chronic myeloid leukemia (chronic-phase), patients with mutations in the BCR-ABL gene fusion kinase domain from … (full text at CIViC) PMID 19779040 · Müller et al., 2009 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Predictive	B	Supports Resistance	2	accepted	EID4368 In a study of 51 imatinib-resistant chronic myeloid leukemia patients, patients with the T315I mutation in the ABL1 portion of the BCR-ABL1 gene fusion (n=13) were associated with acquired resistant t… (full text at CIViC) PMID 27485109 · Soverini et al., 2016 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Predictive	C	Supports Resistance	2	submitted	EID4366 In a retrospective study (of phase 3 clinical trial NCT00481247) of 363 Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia patients in chronic phase, patients with the T315I mutation in t… (full text at CIViC) PMID 26118315 · Hughes et al., 2015 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Predictive	C	Supports Resistance	3	accepted	EID4373 Prior to dasatinib treatment, two imatinib-resistant patients with chronic myeloid leukemia in accelerated phase had the BCR-ABL1 fusion with the T315I secondary variant in 8/10 and 10/10 bacterial cl… (full text at CIViC) PMID 16775234 · Talpaz et al., 2006 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Predictive	D	Does Not Support Resistance	2	submitted	EID4363 In an in vitro kinase study, the recombinant ABL1 H396P mutant kinase did not demonstrate resistance to dasatinib treatment at concentrations of 1μM and 10μM (activity %: 0 and 1) when compared to wil… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Predictive	D	Supports Resistance	2	submitted	EID4367 In an in vitro study, a KBM-5 cell line expressing T315I mutation in the ABL1 portion of the BCR-ABL fusion protein (overexpression) demonstrated resistance to dasatinib treatment, compared to KBM-5 c… (full text at CIViC) PMID 26912052 · Halbach et al., 2016 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib + Imatinib MesylateCombination	Predictive	D	Supports Resistance	2	accepted	EID6192 In an in vitro study, stochastic mutations in the ABL1 region of the p210 BCR-ABL fusion were generated and stably expressed in Ba/F3 cell lines from mutagenized libraries. Combination therapy with 10… (full text at CIViC) PMID 15705718 · Burgess et al., 2005 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib	Predictive	B	Supports Resistance	4	accepted	EID234 In chronic myeloid leukemia patients with the ABL T315I mutation, tumors have shown to be resistant to imatinib treatment. PMID 20537386 · An et al., 2010 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib	Predictive	C	Supports Resistance	3	accepted	EID2668 In this study, patients on imatinib monotherapy were monitored for ABL1 kinase domain variants in BCR-ABL1 fusions amplified from peripheral blood RNA. A late-chronic phase (CP) patient had major cyto… (full text at CIViC) PMID 12623848 · Branford et al., 2003 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib	Predictive	D	Supports Resistance	4	accepted	EID235 COS7 cell lines transfected with BCR-ABL constructs harboring T315I mutations were shown to be resistant to imatinib and exhibited increased kinase activity. PMID 15194504 · Yamamoto et al., 2004 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib	Predictive	D	Supports Resistance	4	accepted	EID2667 A panel of 18 mutations representing 85% of known mutations seen in imatinib CML patents were used to evaluate the effectiveness of drug binding. All mutations were compared with non-mutated BCR-ABL p… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib	Predictive	D	Supports Resistance	4	accepted	EID2669 A panel of 16 mutations seen in imatinib CML patents were used to evaluate the effectiveness of drug binding. All mutations were compared with non-mutated BCR-ABL protein and evaluated for anti-prolif… (full text at CIViC) PMID 15930265 · O'Hare et al., 2005 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib Mesylate	Predictive	C	Supports Resistance	3	accepted	EID6990 In a study of 39 chronic phase CML patients with BCR-ABL variants, T315I was seen in 7 imatinib-resistant patients that were also resistant or intolerant to dasatinib and/or nilotinib treatment. Nine … (full text at CIViC) PMID 22371878 · Khoury et al., 2012 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib Mesylate	Predictive	C	Supports Resistance	1	accepted	EID7038 In a phase II study of 60 imatinib-resistant patients with BCR-ABL mutations, 5 had T315I mutations PMID 17264298 · Guilhot et al., 2007 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib + Imatinib MesylateCombination	Predictive	D	Supports Resistance	3	accepted	EID6234 In an in vitro study, stochastic mutations were introduced into the ABL1 region of a stably expressed p210 BCR-ABL fusion in Ba/F3 cells using N-ethyl-N-nitrosourea mutagenesis. Resulting clones were … (full text at CIViC) PMID 16772610 · Bradeen et al., 2006 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib Mesylate + NilotinibCombination	Predictive	D	Supports Resistance	2	accepted	EID6196 In an in vitro study, stochastic mutations were introduced into the ABL1 region of a stably expressed p210 BCR-ABL fusion in Ba/F3 cells using N-ethyl-N-nitrosourea mutagenesis. Resulting clones were … (full text at CIViC) PMID 16772610 · Bradeen et al., 2006 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib + Imatinib Mesylate + NilotinibSubstitutes	Predictive	D	Supports Resistance	3	accepted	EID6285 In an in vitro study, stochastic mutations were introduced into the ABL1 region of a stably expressed p210 BCR-ABL fusion in Ba/F3 cells using N-ethyl-N-nitrosourea mutagenesis. Resulting clones were … (full text at CIViC) PMID 16772610 · Bradeen et al., 2006 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Nilotinib	Predictive	D	Supports Resistance	4	accepted	EID2670 In an in vitro study, a Ba/F3 cell line stably expressing the T315I mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with resistance to nilotinib treatment (IC50: 39.41-fold… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib + NilotinibCombination	Predictive	D	Supports Resistance	3	accepted	EID6235 In an in vitro study, stochastic mutations were introduced into the ABL1 region of a stably expressed p210 BCR-ABL fusion in Ba/F3 cells using N-ethyl-N-nitrosourea mutagenesis. Resulting clones were … (full text at CIViC) PMID 16772610 · Bradeen et al., 2006 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib + Imatinib + NilotinibSubstitutes	Predictive	D	Supports Resistance	3	accepted	EID7780 Bone marrow mononuclear cells (BM MNCs) were isolated from a chronic myeloid leukemia patients with the BCR-ABL1 T315I variant who was pretreated with imatinib, dasatinib, and chemotherapy. The patien… (full text at CIViC) PMID 25686603 · Pemovska et al., 2015 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Omacetaxine Mepesuccinate	Predictive	B	Supports Sensitivity Response	3	submitted	EID6197 This prospective, multicenter, open-label phase 2 study assessing efficacy of omacetaxine included 62 patients who had been diagnosed with T315I mutations and pretreated with 1 or more tyrosine kinase… (full text at CIViC) PMID 22896000 · Cortes et al., 2012 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Omacetaxine Mepesuccinate	Predictive	D	Supports Sensitivity Response	4	submitted	EID6224 Mice with BCR-ABL induced CML were treated with omacetaxine for 4 days starting on Day 10 after transplantation with murine bone marrow cells transduced with BCR-ABL-T315I retrovirus. 15 mice with pla… (full text at CIViC) PMID 19322212 · Chen et al., 2009 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib	Predictive	B	Supports Sensitivity Response	5	accepted	EID639 Ponatinib has shown to be effective in patients with BCR-ABL kinase domain mutations including T315I. PMID 25349473 · Miller et al., 2014 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib	Predictive	B	Supports Sensitivity Response	4	accepted	EID1390 Study describes a phase 1 clinical trial of ponatinib in treatment of 81 refractory Philadelphia chromosome-positive leukemias. 43 of these patients were considered to have chronic-phase CML. All 12 c… (full text at CIViC) PMID 23190221 · Cortes et al., 2012 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib	Predictive	B	Supports Sensitivity Response	2	submitted	EID2672 In a prospective study (NCT01207440) of 449 previously treated chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia patients, chronic-phase CML patients (n=… (full text at CIViC) PMID 24180494 · Cortes et al., 2013 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib	Predictive	D	Does Not Support Resistance	3	accepted	EID7779 Bone marrow mononuclear cells (BM MNCs) were isolated from a chronic myeloid leukemia patient with the BCR-ABL1 T315I variant. The patient was pretreated with imatinib, dasatinib, and chemotherapy. Th… (full text at CIViC) PMID 25686603 · Pemovska et al., 2015 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I AND ABL1 E255V	Axitinib	Predictive	D	Supports Resistance	2	submitted	EID12312 In an in vitro study, pro-B Ba/F3 cell line expressing a compound mutant of both E255V and T315I mutations in the ABL1 portion of the BCR-ABL1 fusion protein demonstrated resistance to axitinib treatm… (full text at CIViC) PMID 26582647 · Zabriskie et al., 2016 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I AND ABL1 F359V	Axitinib	Predictive	D	Supports Sensitivity Response	2	submitted	EID12316 In an in vitro study, pro-B Ba/F3 cell line expressing a compound mutant of both F359V and T315I mutations in the ABL1 portion of the BCR-ABL1 fusion protein demonstrated increased sensitivity to axit… (full text at CIViC) PMID 26582647 · Zabriskie et al., 2016 · Open in CIViC	civic
BCR::ABL1 Fusion AND ABL1 T315I AND ABL1 G250E	Axitinib	Predictive	D	Supports Resistance	2	submitted	EID12308 In an in vitro study, pro-B Ba/F3 cell line expressing a compound mutant of both G250E and T315I mutations in the ABL1 portion of the BCR-ABL1 fusion protein demonstrated resistance to axitinib treatm… (full text at CIViC) PMID 26582647 · Zabriskie et al., 2016 · Open in CIViC	civic