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Gene Symbol | CBL | ||||||||||
Synonyms | C-CBL | CBL2 | FRA11B | NSLL | RNF55 | ||||||||||
Gene Description | CBL, Cbl proto-oncogene, is an E3 ubiquitin-protein ligase involved in cell signaling and ubiquitination of tyrosine kinases (PMID: 23085373). CBL mutations, often resulting in a loss of function, have been identified primarily in myeloid neoplasms, including myelodysplastic syndrome, acute myeloid leukemia, chronic myeloid leukemia, myelofibrosis, and juvenile myelomonocytic leukemia (PMID: 25477533). | ||||||||||
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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CBL Y371H FLT3 wild-type | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Y371H FLT3 wild-type | hematologic cancer | sensitive | Midostaurin | Preclinical | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture, reduced leukemia burden and prolonged survival in animal models (PMID: 31309543). | 31309543 |
CBL Y371H FLT3 wild-type | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Y371H FLT3 wild-type | hematologic cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Y371H FLT3 wild-type | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Y371H FLT3 wild-type | hematologic cancer | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). | 31309543 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture, and inhibited leukemic growth and prolonged survival in cell line xenograft models expressing FLT3 and CBL Y371H (PMID: 31943762). | 31943762 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | Midostaurin + PRT062607 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | PRT062607 + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Nexavar (sorafenib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H FLT3 pos | hematologic cancer | sensitive | PRT062607 + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Quizartinib (AC220) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture, and inhibited leukemic growth and prolonged survival in cell line xenograft models expressing FLT3 and CBL Q365_E366insSK (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Midostaurin + PRT062607 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | PRT062607 + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Nexavar (sorafenib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | PRT062607 + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Quizartinib (AC220) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Crenolanib + PRT062607 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Crenolanib resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Gilteritinib + PRT062607 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Xospata (gilteritinib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Entospletinib + Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Entospletinib to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL mutant | bone marrow cancer | sensitive | Quizartinib | Preclinical | Actionable | In a preclinical study, Quizartinib (AC220) reduced white blood cell counts and decreased myeloid cell invasion in a CBL mutant mouse model with myeloproliferative disorder (PMID: 22990016). | 22990016 |
BRAF G469A CBL C404Y FLT3 exon 14 ins FLT3 D835X | acute myeloid leukemia | predicted - resistant | Gilteritinib | Case Reports/Case Series | Actionable | In a clinical study, a patient with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and was found to have acquired CBL C404Y and BRAF G469A (PMID: 31088841). | 31088841 |
BRAF V600E CBL dec exp | high grade glioma | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, siRNA mediated knockdown of CBL in glioma cell lines harboring BRAF V600E prevented Zelboraf (vemurafenib)-mediated inhibition of cell growth in culture (PMID: 34433654). | 34433654 |
BRAF V600E CBL dec exp | high grade glioma | predicted - resistant | Neratinib | Preclinical - Cell culture | Actionable | In a preclinical study, glioma cell lines harboring BRAF V600E and siRNA mediated knockdown of CBL were resistant to treatment with Nerlynx (neratinib) in culture (PMID: 34433654). | 34433654 |
BRAF V600E CBL dec exp | high grade glioma | predicted - resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, glioma cell lines harboring BRAF V600E and siRNA mediated knockdown of CBL were resistant to treatment with Cotellic (cobimetinib) in culture (PMID: 34433654). | 34433654 |
CBL Y371del FLT3 pos | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). | 31943762 |
CBL Y371del FLT3 pos | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). | 31943762 |
CBL Y371del FLT3 pos | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). | 31943762 |
CBL Y371del FLT3 pos | hematologic cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). | 31943762 |
CBL Y371del FLT3 pos | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). | 31943762 |
CBL Y371del FLT3 pos | hematologic cancer | sensitive | Midostaurin + PRT062607 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). | 31943762 |
CBL Q367_E373delinsRLK FLT3 exon 14 ins FLT3 D835X NRAS G12D | acute myeloid leukemia | predicted - resistant | Gilteritinib | Case Reports/Case Series | Actionable | In a clinical study, a patient with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and was found to have acquired NRAS G12D and CBL Q367_E373delinsRLK (PMID: 31088841). | 31088841 |
CBL dec exp | pancreatic ductal carcinoma | predicted - sensitive | Erlotinib + Gemcitabine | Preclinical - Cell line xenograft | Emerging | In a preclinical study, addition of Tarceva (erlotinib) overcame Gemzar (gemcitabine)-resistance in pancreatic ductal carcinoma cell lines with reduced Cbl expression via shRNA, resulted in decreased viability in cell culture and reduced tumor growth in cell line xenograft models (PMID: 25348515). | 25348515 |
CBL mutant | systemic mastocytosis | not applicable | N/A | Guideline | Prognostic | CBL mutations are associated with an adverse prognosis in patients with systemic mastocytosis (NCCN.org). | detail... |
CBL mutant | myelofibrosis | not applicable | N/A | Guideline | Prognostic | CBL mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org). | detail... |
CBL mutant | myelodysplastic/myeloproliferative neoplasm | not applicable | N/A | Clinical Study | Prognostic | In clinical analyses, mutations in CBL were associated with adverse prognosis in patients with chronic myelomonocytic leukemia (PMID: 26230957, PMID: 23690417, PMID: 19901108). | 26230957 19901108 23690417 |