Molecular Subtype
Chronic Myeloid Leukemia, BCR-ABL1 Positive
CI-CAN-00002365CMLExplore in graph →
Hematologic102 active trials3 approved drugs320 evidence items
- NCIt
- C3174
- OncoTree
- CMLBCRABL1
- DOID
- 0081088
- DOID
- 8552
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Molecular Subtype
CI-CAN-00002365CMLExplore in graph →
Variants & evidence
522 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|
| ABL1 V299L + ABL1 Fusion7 | |||||||
| Dasatinib | Predictive | C | Supports Resistance | 3 | accepted | EID4541In a study of 51 imatinib-resistant chronic myeloid leukemia patients, patients with the V299L mutation in the ABL1 portion of the BCR-ABL1 gene fusion (n=3) were associated with acquired resistant to… (full text at CIViC) PMID 27485109 · Soverini et al., 2016 · Open in CIViC | civic |
| 〃 | Predictive | C | Supports Resistance | 1 | accepted | EID4540This 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 |
| 〃 | Predictive | D | Supports Resistance | 3 | accepted | EID6216In an in vitro study, stochastic mutations in the ABL1 region of a stably expressed p210 BCR-ABL fusion were generated in Ba/F3 cell lines from five independently derived, mutagenized libraries. Dasat… (full text at CIViC) PMID 15705718 · Burgess et al., 2005 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 2 | accepted | EID6247In 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 |
| Imatinib Mesylate | Predictive | B | Supports Resistance | 1 | accepted | EID6982In a study of 39 chronic phase CML patients with BCR-ABL variants, V299L was seen in two imatinib-resistant patients that were also resistant or intolerant to dasatinib and/or nilotinib treatment. Nin… (full text at CIViC) PMID 22371878 · Khoury et al., 2012 · Open in CIViC | civic |
| Dasatinib + Imatinib MesylateCombination | Predictive | D | Supports Resistance | 2 | accepted | EID6241In 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 |
| Nilotinib | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID2862In an in vitro study, a Ba/F3 cell line stably expressing the V299L mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to nilotinib treatment (IC50: 1.34-fold)… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC | civic |
| ABL1 V379I + ABL1 Fusion5 | |||||||
| Dasatinib | Predictive | C | Does Not Support Resistance | 3 | accepted | EID4702Prior to dasatinib treatment, one imatinib-resistant patient with chronic myeloid leukemia in accelerated phase had the BCR-ABL1 fusion with E279K, V379I, and V379I/F317L/M351T variants in 3/11, 5/11,… (full text at CIViC) PMID 16775234 · Talpaz et al., 2006 · Open in CIViC | civic |
| 〃 | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID4703In a retrospective study of 174 imatinib-resistant or -intolerant Philadelphia chromosome BCR-ABL1 fusion positive accelerated phase chronic myeloid leukemia patients, patients with mutations in the A… (full text at CIViC) PMID 19487385 · Apperley et al., 2009 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 1 | submitted | EID4705In an in vitro study, a Ba/F3 cell line expressing a V379I mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to dasatinib treatment (0.8 nmol/L vs. 0.8 nmol/L… | |
| ABL1 Y253F + ABL1 Fusion12 | |||||||
| Axitinib | Predictive | D | Supports Resistance | 2 | accepted | EID4345In a proliferation assay measuring tritiated thymidine incorporation in the presence of axitinib, Ba/F3 cells carrying the BCR-ABL1 variant showed increased incorporation when harboring fusions with t… (full text at CIViC) PMID 25686603 · Pemovska et al., 2015 · Open in CIViC | civic |
| Bosutinib | Predictive | C | Does Not Support Resistance | 1 | accepted | EID4340In 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 |
| 〃 | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID4339In an in vitro study, a Ba/F3 murine cell line stably expressing the Y253F mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to bosutinib treatment (IC50: 40n… | |
| ABL1 Y253H + ABL1 Fusion16 | |||||||
| Axitinib | Predictive | D | Does Not Support Resistance | 2 | accepted | EID4329In a proliferation assay measuring tritiated thymidine incorporation in the presence of axitinib, Ba/F3 cells carrying the BCR-ABL1 variant showed similar incorporation when harboring fusions with the… (full text at CIViC) PMID 25686603 · Pemovska et al., 2015 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 2 | accepted | EID4330In an in vitro study, pro-B Ba/F3 cell line expressing Y253H mutation in the ABL1 portion of the BCR-ABL1 fusion protein (overexpression) demonstrated resistance to axitinib treatment (IC50: 1069.7nM)… (full text at CIViC) PMID 26582647 · Zabriskie et al., 2016 · Open in CIViC | civic |
| Bosutinib | Predictive | C | Does Not Support Resistance | 3 | accepted | EID4332This 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… | |
| ABL1 E255V + ABL1 Y253H + ABL1 Fusion1 | |||||||
| Axitinib | Predictive | D | Supports Resistance | 2 | submitted | EID12313In an in vitro study, pro-B Ba/F3 cell line expressing a compound mutant of both E255V and Y253H 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 |
| EGFR T790M1 | |||||||
| Bosutinib | Predictive | D | Does Not Support Resistance | 2 | submitted | EID3812In an in vitro kinase study, the recombinant ABL1 M351T mutant kinase did not demonstrate resistance to bosutinib treatment at concentrations of 1μM and 10μM (activity %: 2 and 0) when compared to wil… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| FGFR1 V561M2 | |||||||
| Bosutinib | Predictive | D | Supports Resistance | 2 | submitted | EID7512In an in vitro kinase study, the recombinant FGFR1 V561M mutant kinase demonstrated resistance to bosutinib treatment at concentrations of 1μM and 10μM (activity %: 87 and 41) when compared to wild ty… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| Dasatinib | Predictive | D | Supports Resistance | 2 | submitted | EID7513In an in vitro kinase study, the recombinant FGFR1 V561M mutant kinase demonstrated resistance to dasatinib treatment at concentrations of 1μM and 10μM (activity %: 100 and 64) when compared to wild t… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| FGFR2 N549H2 | |||||||
| Bosutinib | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID7510In an in vitro kinase study, the recombinant FGFR2 N549H mutant kinase demonstrated sensitivity to bosutinib treatment at concentrations of 1μM and 10μM (activity %: 32 and 3) when compared to wild ty… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| Dasatinib | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID7511In an in vitro kinase study, the recombinant FGFR2 N549H mutant kinase demonstrated sensitivity to dasatinib treatment at concentrations of 1μM and 10μM (activity %: 6 and -1) when compared to wild ty… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| FLT3 G73E1 | |||||||
| (oncogenic) | Oncogenic | C | Supports Oncogenicity | 2 | rejected | EID12426The variant was identified by NGS in a CML (unmatched analysis) (Supplementary File 2). PMID 32943879 · Wu et al., 2020 · Open in CIViC | civic |
| JAK2 V617F2 | |||||||
| (diagnostic) | Diagnostic | B | Supports Positive | 4 | accepted | EID5JAK2 V617F is associated with myeloid malignanices (AML, MDS, CMML/atypical CML). PMID 16081687 · Levine et al., 2005 · Open in CIViC | civic |
| 〃 | Diagnostic | B | Supports Positive | 4 | accepted | EID6JAK2 V617F is associated with myeloid neoplasms (AML, MDS, CMML/aCML). PMID 16081687 · Levine et al., 2005 · Open in CIViC | civic |
| RET Fusion + RET V804L1 | |||||||
| Dasatinib | Predictive | D | Supports Resistance | 2 | submitted | EID7515In an in vitro kinase study, the recombinant RET V804L mutant kinase demonstrated resistance to dasatinib treatment at concentrations of 1μM and 10μM (activity %: 101 and 91) when compared to wild typ… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
Data updated 20 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
PMID 15930265 · O'Hare et al., 2005 · Open in CIViC
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| Imatinib Mesylate | Predictive | C | Supports Resistance | 3 | accepted | EID7033In a phase II study of 60 imatinib-resistant patients with BCR-ABL mutations, 4 had V379I mutations PMID 17264298 · Guilhot et al., 2007 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 2 | accepted | EID6257In 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 |
PMID 19075254 · Redaelli et al., 2009 · Open in CIViC
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| 〃 | Predictive | D | Does Not Support Resistance | 2 | submitted | EID7508In an in vitro kinase study, the recombinant ABL1 Y253F mutant kinase did not demonstrate resistance to bosutinib treatment at concentrations of 1μM and 10μM (activity %: 1 and 0) when compared to wil… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| Dasatinib | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID4343In a retrospective study of 1084 imatinib-resistant or -intolerant, chronic myeloid leukemia (chronic-phase) patients, patients with a mutation in the ABL1 portion of the BCR-ABL gene fusion were asso… (full text at CIViC) PMID 19779040 · Müller et al., 2009 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID4341In an in vitro study, a Ba/F3 cell line stably expressing the Y253F mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to dasatinib treatment (IC50: 2.89nM vs… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID4342In an in vitro study, a Ba/F3 cell line expressing a Y253F mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to dasatinib treatment (1.4 nmol/L vs. 0.8 nmol/L… (full text at CIViC) PMID 15930265 · O'Hare et al., 2005 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID4344In an in vitro study, a Ba/F3 cell line stably expressing the Y253F mutation in the ABL1 portion of the BCR-ABL1 fusion protein was found to have increased sensitivity to dasatinib treatment, as comp… (full text at CIViC) PMID 15256671 · Shah et al., 2004 · Open in CIViC | civic |
| 〃 | Predictive | D | Does Not Support Resistance | 2 | submitted | EID7509In an in vitro kinase study, the recombinant ABL1 Y253F mutant kinase did not demonstrate resistance to dasatinib treatment at concentrations of 1μM and 10μM (activity %: -1 and 1) when compared to wi… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC | civic |
| Imatinib | Predictive | C | Supports Resistance | 3 | accepted | EID8508In this study, patients on imatinib monotherapy were monitored for ABL1 kinase domain variants in BCR-ABL1 fusions amplified from peripheral blood RNA. An AP patient had a complete hematologic respons… (full text at CIViC) PMID 12623848 · Branford et al., 2003 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 3 | accepted | EID2657In two cell-based studies, a panel of either 18 or 16 mutations representing 85% of known mutations seen in imatinib CML patents were used to evaluate the effectiveness of drug binding. All mutations … (full text at CIViC) PMID 15930265 · O'Hare et al., 2005 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 2 | accepted | EID2655A 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 |
PMID 22371878 · Khoury et al., 2012 · Open in CIViC
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| 〃 | Predictive | C | Does Not Support Resistance | 2 | accepted | EID4331In 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 |
| Dasatinib | Predictive | B | Does Not Support Resistance | 3 | accepted | EID4335This 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 |
| 〃 | Predictive | C | Does Not Support Resistance | 4 | accepted | EID4336Prior to dasatinib treatment, one imatinib-resistant patient with chronic myeloid leukemia in chronic phase had the BCR-ABL1 fusion with the Y253H secondary variant in 11/11 bacterial clones generated… (full text at CIViC) PMID 16775234 · Talpaz et al., 2006 · Open in CIViC | civic |
| 〃 | Predictive | C | Does Not Support Resistance | 3 | accepted | EID7949Prior to dasatinib treatment, one imatinib-resistant patient with chronic myeloid leukemia in chronic phase had the BCR-ABL1 fusion with Y253H, M388L, and M388L/M244V variants in 4/10, 5/10, and 1/10 … (full text at CIViC) PMID 16775234 · Talpaz et al., 2006 · Open in CIViC | civic |
| 〃 | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID4333In a retrospective study of 174 imatinib-resistant or -intolerant Philadelphia chromosome BCR-ABL1 fusion positive accelerated phase chronic myeloid leukemia patients, patients with mutations in the A… (full text at CIViC) PMID 19487385 · Apperley et al., 2009 · Open in CIViC | civic |
| 〃 | Predictive | C | Does Not Support Resistance | 1 | accepted | EID4334In this phase II multinational study, 60 imatinib-resistant patients with accelerated phase CML and BCR-ABL fusions were treated with dasatinib monotherapy. 44 (73%) of 60 BCR-ABL mutant patients achi… (full text at CIViC) PMID 17264298 · Guilhot et al., 2007 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4337In an in vitro study, a Ba/F3 cell line stably expressing the Y253H mutation in the ABL1 portion of the BCR-ABL1 fusion protein was found to have increased sensitivity to dasatinib treatment, as compa… (full text at CIViC) PMID 15256671 · Shah et al., 2004 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4338In an in vitro study, a Ba/F3 cell line expressing a Y253H mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to dasatinib treatment (1.3 nmol/L vs. 0.8 nmol/L… (full text at CIViC) PMID 15930265 · O'Hare et al., 2005 · Open in CIViC | civic |
| Imatinib Mesylate | Predictive | B | Supports Resistance | 1 | accepted | EID7040In a phase II study of 60 imatinib-resistant patients with BCR-ABL mutations, 6 had Y253H mutations PMID 17264298 · Guilhot et al., 2007 · Open in CIViC | civic |
| 〃 | Predictive | C | Supports Resistance | 3 | accepted | EID6992In a study of 39 chronic phase CML patients with BCR-ABL variants, Y253H was seen in 6 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 |
| Imatinib Mesylate + NilotinibCombination | Predictive | D | Supports Resistance | 2 | accepted | EID6237In 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 |
| Imatinib Mesylate + NilotinibSubstitutes | Predictive | C | Supports Resistance | 3 | accepted | EID6200In this open-label, phase II registration trial, patients that were imatinib resistant or intolerant underwent nilotinib monotherapy. Within 12 months of nilotinib therapy, there was no significant di… (full text at CIViC) PMID 19652056 · Hughes et al., 2009 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 3 | accepted | EID2654In an in vitro study, a Ba/F3-p210BCR-ABL1 cell line was ENU-mutated and exposed to graded concentrations of imatinib, nilotinib or dasatinib to identify resistance mutations. The Y253H mutation in th… (full text at CIViC) PMID 16772610 · Bradeen et al., 2006 · Open in CIViC | civic |