Result
| Gene | Variant | Type | Tumor | Drug | Drug level | Reference | More | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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| ABL1 | ABL1-. | FUS | Acute Lymphoblastic Leukemia | TK Inhibitors | IV | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
Literature Patient Criteria- NoteIn conclusion, we report the largest cohort of patients with ABL-class kinase rearrangement exposed to TKI frontline or at relapse, and show promising MRD response and outcome, reminiscent of those observed in early trials of imatinib combined with chemotherapy in Ph+ ALL.18 Prospective screening strategies are feasible and should be generalized to identify these high-risk patients and to propose early TKI-based intervention. In future studies, several questions remain to be addressed, including the choice of TKI according to the fusion transcript, whether these patients should receive recently approved blinatumomab,19 and finally the benefit of HSCT in patients who achieve good MRD response upon targeted therapy. Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Sorry, there is no related drug information. |
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| ABL1 | ABL1-. | FUS | Acute Lymphoblastic Leukemia | TK Inhibitors | II | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
Literature Patient Criteria NoteIn conclusion, ABL-class fusions are frequent among BCP and T-ALL patients who respond slowly to induction therapy. We have demonstrated a reduced risk of relapse for ABL-class fusion patients with EOI MRD _1% treated with adjuvant TKI without a significant increased risk of severe toxicity. The ALLTogether 01 trial (EUDRACT number: 2018-001795-38) will screen patients at diagnosis for ABL-class fusions and add imatinib from day 15 (day 28 if aged _16 years) to a standard chemotherapy backbone to investigate whether early TKI reduces EOI MRD and improves outcome for all patients with an ABL-class fusion. Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Sorry, there is no related drug information. |
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| ABL1 | ABL1-BCR | FUS | Acute Lymphoblastic Leukemia | Dasatinib | I | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- Note- Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Dasatinib DrugBank ID Synonymsanh. dasatinib Apo-dasatinib Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCRABL, SRC, Ephrins and GFR. Target gene
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| ABL1 | ABL1-BCR | FUS | Acute Lymphoblastic Leukemia | Dasatinib+Venetoclax | V | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- NoteEvaluation of the dasatinib-venetoclax combination for the treatment of primary Ph+ALL patient samples in xenografted immunodeficient mice confirmed the tolerability of this drug combination and demonstrated its superior antileukemic efficacy compared to either agent alone. These data suggest that the combination of dasatinib and venetoclax has the potential to improve the treatment of Ph+ALL and should be further evaluated for patient care. Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Dasatinib DrugBank ID Synonymsanh. dasatinib Apo-dasatinib Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCRABL, SRC, Ephrins and GFR. Target gene
Drug name Venetoclax DrugBank ID Synonyms4-{4-[(4'-chloro-5,5-dimethyl[3,4,5,6-tetrahydro[1,1'-biphenyl]]-2-yl)methyl]piperazin-1-yl}-N-(3-nitro-4-{[(oxan-4-yl)methyl]amino}benzene-1-sulfonyl)-2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide Venclyxto Venetoclax is a BCL-2 inhibitor that was initially approved by the FDA in April 2016 [FDA label]. Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are important regulators of the apoptotic (programmed cell death) process [A18565], [A18566]. Venetoclax is used to treat chronic lymphocytic leukemia (CLL) and certain types of small lymphocytic lymphoma [FDA label]. CLL is the most prevalent leukemia diagnosed in Western countries [A40022]. Venetoclax was developed through reverse engineering of the BCL-2 protein family inhibitor, navitoclax [A40022]. Venetoclax is approximately 10 times more potent than navitoclax with regard to induction of apoptosis in CLL cells [A40022]. A new indication was approved in 2018 for the treatment patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy [FDA label]. Previously, this drug was indicated only for patients with 17p gene deletion [F2130]. Target gene
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| ABL1 | ABL1-BCR | FUS | Acute Lymphoblastic Leukemia | Imatinib | I | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- Note- Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Imatinib DrugBank ID SynonymsImatinib Imatinib Teva Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells. Target gene
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| ABL1 | ABL1-BCR | FUS | Acute Lymphoblastic Leukemia | Ponatinib | I | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- Note- Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Ponatinib DrugBank ID SynonymsPonatinib Iclusig DescriptionPonatinib is a novel Bcr-Abl tyrosine kinase inhibitor that is especially effective against the T315I mutation for the treatment of chronic myeloid leukemia. FDA approved on December 14, 2012. Target gene
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| ABL1 | ABL1-BCR | FUS | Acute Lymphoblastic Leukemia | Axitinib | RIII | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
CIVIC Patient CriteriaT315I NoteBone 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. 2/3 patient's BM MNCs were considered sensitive to ponatinib and axitinib using drug sensitivity scoring of proliferation assays. Additionally, BCR-ABL T315I showed sensitivity to ponitinib and axitinib in Ba/F3 cells. Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Axitinib DrugBank ID SynonymsAxitinib Inlyta DescriptionAxitinib is a second generation tyrosine kinase inhibitor that works by selectively inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3).[L6676] Through this mechanism of action, axitinib blocks angiogenesis, tumour growth and metastases. It is reported to exhibit potency that is 50-450 times higher than that of the first generation VEGFR inhibitors.[L6676] Axitinib is an indazole derivative.[A179398] It is most commonly marketed under the name Inlyta® and is available in oral formulations. Target gene
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| ABL1 | ABL1-BCR | FUS | Acute Lymphoblastic Leukemia | Dasatinib | IV | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
CIVIC Patient Criteria- NotePrior to dasatinib treatment, one imatinib-resistant patient with acute lymphoblastic leukemia had the BCR-ABL1 fusion with no secondary variants in at least ten bacterial clones generated using peripheral blood RNA. They had NEL (no evidence of leukemia) best hematologic and minor best cytogenetic responses to dasatinib. Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Dasatinib DrugBank ID Synonymsanh. dasatinib Apo-dasatinib Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCRABL, SRC, Ephrins and GFR. Target gene
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| ABL1 | ABL1-BCR | FUS | Acute Lymphoblastic Leukemia | Dasatinib | RII | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
CIVIC Patient CriteriaE255K NotePrior to dasatinib treatment, one imatinib-resistant patient with acute lymphoblastic leukemia had the BCR-ABL1 fusion with the E255K secondary variant in 3/12 bacterial clones generated using peripheral blood RNA. They had no best hematologic and no best cytogenetic responses to dasatinib which were worse compared to responses in patient with unmutated BCR-ABL1. Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Dasatinib DrugBank ID Synonymsanh. dasatinib Apo-dasatinib Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCRABL, SRC, Ephrins and GFR. Target gene
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| ABL1 | ABL1-BCR | FUS | Acute Lymphoblastic Leukemia | Dasatinib | RII | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Evidence region
CIVIC Patient CriteriaT315I NoteIn 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 mutations did not differ from the rate of the total population of 100 imatinib-resistant or -intolerant patients. 44 (73%) of 60 BCR-ABL mutant patients achieved major hematologic responses (MaHRs) and 18 (30%) of 60 achieved major cytogenetic responses (MCyRs). Of patients with T315I, 0/5 had MaHRs and 0/5 had MCyRs which were lower than response rates among wild type patients. Gene name
Full name
ABL proto-oncogene 1, non-receptor tyrosine kinase Gene typeprotein-coding FunctionThis gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014] Drug name
Dasatinib DrugBank ID Synonymsanh. dasatinib Apo-dasatinib Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCRABL, SRC, Ephrins and GFR. Target gene
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