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 D276G + ABL1 Fusion3 | |||||||
| Imatinib | Predictive | D | Supports Resistance | 2 | accepted | EID2663A 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 |
| Imatinib Mesylate | Predictive | D | Supports Resistance | 2 | accepted | EID6246In 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 | 2 | accepted | EID2666In an in vitro study, a Ba/F3 cell line stably expressing the D276G mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to nilotinib treatment (IC50: 2.00-fold… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC | civic |
| ABL1 D363G + ABL1 Fusion2 | |||||||
| Dasatinib | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID4692Prior to dasatinib treatment, one imatinib-resistant patient with chronic myeloid leukemia in chronic phase had the BCR-ABL1 fusion with the D363G secondary variant in 2/10 bacterial clones generated … (full text at CIViC) PMID 16775234 · Talpaz et al., 2006 · Open in CIViC | civic |
| Imatinib | Predictive | C | Supports Resistance | 1 | accepted | EID7820One chronic myeloid leukemia patient in chronic phase had a partial best cytogenetic response to imatinib but became resistant. Bacterial clones generated using peripheral blood RNA revealed the BCR-A… (full text at CIViC) PMID 16775234 · Talpaz et al., 2006 · Open in CIViC | civic |
| ABL1 D421G + ABL1 Fusion1 | |||||||
| Bosutinib | Predictive | C | Supports Sensitivity Response | 1 | accepted | EID4559In 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 |
| ABL1 E255K + ABL1 Fusion22 | |||||||
| Axitinib | Predictive | D | Supports Resistance | 2 | accepted | EID4355In 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 | Supports Resistance | 1 | accepted | EID4347This 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 |
| 〃 | Predictive | C | Does Not Support Resistance | 1 | accepted | EID4348In 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… | |
| ABL1 E255K + ABL1 V299L + ABL1 Fusion1 | |||||||
| Dasatinib + PonatinibSubstitutes | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID7781Bone marrow mononuclear cells isolated from a chronic myeloid leukemia patient with the BCR-ABL1 fusion and E255K and V299L secondary variants in ABL1 showed a high drug sensitivity score to ponatinib… (full text at CIViC) PMID 25686603 · Pemovska et al., 2015 · Open in CIViC | civic |
| ABL1 E255V + ABL1 Fusion17 | |||||||
| Axitinib | Predictive | D | Supports Resistance | 2 | accepted | EID4441In 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 |
| 〃 | Predictive | D | Supports Resistance | 2 | accepted | EID4442In an in vitro study, a pro-B Ba/F3 cell line expressing E255V mutation in the ABL1 portion of the BCR-ABL1 fusion protein (overexpression) demonstrated resistance to axitinib treatment (IC50: 1015nM)… (full text at CIViC) PMID 26582647 · Zabriskie et al., 2016 · Open in CIViC | civic |
| Bosutinib | Predictive | C | Does Not Support Resistance | 2 | accepted | EID4443In 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… | |
| ABL1 E255V + ABL1 V299L + ABL1 Fusion1 | |||||||
| Axitinib | Predictive | D | Supports Resistance | 2 | submitted | EID12314In an in vitro study, pro-B Ba/F3 cell line expressing a compound mutant of both E255V and V299L 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 |
| ABL1 E279K + ABL1 Fusion3 | |||||||
| Axitinib | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID7772In 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 |
| Bosutinib | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4542In an in vitro study, a Ba/F3 murine cell line stably expressing the E279K mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to bosutinib treatment (IC50: 39.… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC | civic |
| Dasatinib | Predictive | C | Does Not Support Resistance | 3 | accepted | EID4543This 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 … | |
Data updated 25 minutes 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 21865346 · Cortes et al., 2011 · Open in CIViC
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| 〃 | Predictive | D | Supports Resistance | 2 | submitted | EID4346In an in vitro study, a Ba/F3 murine cell line stably expressing the E255K 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 |
| Dasatinib | Predictive | B | Does Not Support Resistance | 3 | accepted | EID4350This 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 | 3 | accepted | EID4353Prior to dasatinib treatment, one imatinib-resistant patient with chronic myeloid leukemia in chronic phase had the BCR-ABL1 fusion with the E255K secondary variant in 12/12 bacterial clones generated… (full text at CIViC) PMID 16775234 · Talpaz et al., 2006 · Open in CIViC | civic |
| 〃 | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID4351In 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 | Supports Reduced Sensitivity | 1 | accepted | EID4352In this phase II multinational study, patients with accelerated phase CML and BCR-ABL fusions were treated with dasatinib monotherapy. Response rate among 60 imatinib-resistant patients with BCR-ABL m… (full text at CIViC) PMID 17264298 · Guilhot et al., 2007 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4349In an in vitro study, a Ba/F3 cell line expressing an E255K mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to dasatinib treatment (5.6 nmol/L vs. 0.8 nmol/… (full text at CIViC) PMID 15930265 · O'Hare et al., 2005 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4354In an in vitro study, a Ba/F3 cell line stably expressing the E255K 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 |
| Dasatinib + Imatinib MesylateSubstitutes | Predictive | D | Supports Resistance | 3 | accepted | EID6214In 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 |
| Imatinib | Predictive | C | Supports Resistance | 4 | accepted | EID2660In 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 patient had a complete hema… (full text at CIViC) PMID 12623848 · Branford et al., 2003 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 4 | accepted | EID233COS7 cell lines transfected with BCR-ABL constructs harboring E255K mutations were shown to be resistant to imatinib and exhibited increased kinase activity. PMID 15194504 · Yamamoto et al., 2004 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 3 | accepted | EID2659A 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 |
| 〃 | Predictive | D | Supports Resistance | 3 | accepted | EID2661A 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 |
| Imatinib Mesylate | Predictive | C | Supports Resistance | 1 | accepted | EID6991In a study of 39 chronic phase CML patients with BCR-ABL variants, E255K was seen in a single imatinib-resistant patient that was also resistant or intolerant to dasatinib and/or nilotinib treatment. … (full text at CIViC) PMID 22371878 · Khoury et al., 2012 · Open in CIViC | civic |
| 〃 | Predictive | C | Supports Resistance | 1 | accepted | EID7039In a phase II study of 60 imatinib-resistant patients with BCR-ABL mutations, 6 had E255K mutations PMID 17264298 · Guilhot et al., 2007 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Resistance | 2 | accepted | EID6282In 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 |
| Dasatinib + Imatinib MesylateCombination | Predictive | D | Supports Resistance | 2 | accepted | EID6193In 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 |
| Nilotinib | Predictive | D | Supports Resistance | 2 | accepted | EID2662In an in vitro study, Ba/F3 cell line stably expressing the E255K mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with resistance to nilotinib treatment (IC50: 6.69-fold), a… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC | civic |
| Dasatinib + Imatinib Mesylate + NilotinibSubstitutes | Predictive | D | Supports Resistance | 2 | accepted | EID6194In 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 | EID6232In 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 |
PMID 21865346 · Cortes et al., 2011 · Open in CIViC
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| 〃 | Predictive | C | Supports Reduced Sensitivity | 1 | accepted | EID4444This 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 |
| 〃 | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4445In an in vitro study, a Ba/F3 murine cell line stably expressing the E255V 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 |
| Dasatinib | Predictive | B | Does Not Support Resistance | 3 | accepted | EID4447This 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 | 3 | accepted | EID4448Three chronic myeloid leukemia patients had the BCR-ABL1 fusion with the E255V secondary variant in one or more bacterial clones generated using peripheral blood RNA. They had no best cytogenetic resp… (full text at CIViC) PMID 16775234 · Talpaz et al., 2006 · Open in CIViC | civic |
| 〃 | Predictive | C | Does Not Support Resistance | 1 | submitted | EID4446In this phase II multinational study, patients with accelerated phase CML and BCR-ABL fusions were treated with dasatinib monotherapy. Response rate among 60 imatinib-resistant patients with BCR-ABL m… (full text at CIViC) PMID 17264298 · Guilhot et al., 2007 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4449In an in vitro study, a Ba/F3 cell line stably expressing the E255V 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 | Supports Sensitivity Response | 2 | submitted | EID4450In an in vitro study, a Ba/F3 cell line expressing an E255V mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with sensitivity to dasatinib treatment (11.0 nmol/L vs. 0.8 nmol… (full text at CIViC) PMID 15930265 · O'Hare et al., 2005 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4451In an in vitro study, a Ba/F3 cell line stably expressing the E255V mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with reduced sensitivity to dasatinib treatment (IC50: 6.… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC | civic |
| Imatinib | Predictive | C | Supports Resistance | 3 | accepted | EID2656In 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 |
| Imatinib Mesylate | Predictive | C | Supports Resistance | 2 | submitted | EID7245In a phase II study of 60 imatinib-resistant patients with BCR-ABL mutations, 2 had E255V mutations. PMID 17264298 · Guilhot et al., 2007 · Open in CIViC | civic |
| 〃 | Predictive | C | Supports Resistance | 1 | accepted | EID6986In a study of 39 chronic phase CML patients with BCR-ABL variants, E255V was seen in a single imatinib-resistant patient that was also resistant or intolerant to dasatinib and/or nilotinib treatment. … (full text at CIViC) PMID 22371878 · Khoury et al., 2012 · Open in CIViC | civic |
| Nilotinib | Predictive | D | Supports Resistance | 3 | accepted | EID2850In an in vitro study, a Ba/F3 cell line stably expressing the E255V mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with resistance to nilotinib treatment (IC50: 10.31-fold… (full text at CIViC) PMID 19075254 · Redaelli et al., 2009 · Open in CIViC | civic |
| Imatinib Mesylate + NilotinibSubstitutes | Predictive | C | Supports Resistance | 3 | accepted | EID6971In 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 | 2 | accepted | EID2851In 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 E255V mutation in th… (full text at CIViC) PMID 16772610 · Bradeen et al., 2006 · Open in CIViC | civic |
PMID 19779040 · Müller et al., 2009 · Open in CIViC
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