Hematologic Malignancy
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
CI-CAN-00000765Explore in graph →
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Hematologic Malignancy
CI-CAN-00000765Explore in graph →
Variants & evidence
82 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| BIRC3 TRUNCATING MUTATION1 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 2 | accepted | EID1488BIRC3 mutations were identified in 23 of 919 screened CLLs. They are strongly linked to non-mutated IGHV genes (18/23, P = 0.0001), a widely recognized prognostic signature for poor outcome. PMID 24943832 · Baliakas et al., 2015 · Open in CIViC | civic |
| BTK C481R1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia | Predictive | C | Does Not Support Resistance | 2 | submitted | EID10374The effective cohort in this study was 11 CLL patients who were first treated with ibrutinib and then on progression treated with venetoclax until progression. Patient samples were sequenced before an… (full text at CIViC) PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| BTK C481S2 | ||||||||
| Ibrutinib | Chronic Lymphocytic Leukemia | Predictive | B | Supports Resistance | 4 | accepted | EID436Whole exome sequencing of 6 chronic lymphocytic leukemia patients with acquired resistance to ibrutinib determined 5/6 patients harbored a C481S mutation in BTK. PMID 24869598 · Woyach et al., 2014 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Predictive | B | Supports Resistance | 4 | accepted | EID1770In a trial of 308 patients with chronic lymphocytic leukemia treated with ibrutinib, 31 discontinued treatment due to disease progression (13 CLL progression, 18 Richter’s transformation). 11/13 patie… (full text at CIViC) PMID 26182309 · Maddocks et al., 2015 · Open in CIViC | civic |
| BTK C481Y1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia | Predictive | C | Supports Resistance | 2 | submitted | EID10373The effective cohort in this study was 11 CLL patients who were first treated with ibrutinib and then on progression treated with venetoclax until progression. Patient samples were sequenced before an… (full text at CIViC) PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| BTK MUTATION1 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID5833A patient cohort of 308 individuals was created from trials of Ibrutinib in CLL (see Maddocks 2015, PMID: 26182309). A secondary cohort was created from a prospective collection of 112 patients. 83/… (full text at CIViC) PMID 28418267 · Woyach et al., 2017 · Open in CIViC | civic |
| BTK T316A1 | ||||||||
| Ibrutinib | Chronic Lymphocytic Leukemia | Predictive | C | Supports Resistance | 4 | accepted | EID1985Case report of a patient with CLL and Richter-transformed relapse under ibrutinib (after an initial partial response for 10 months). Sequencing of sequential samples of this patient revealed a novel B… (full text at CIViC) PMID 27626698 · Sharma et al., 2016 · Open in CIViC | civic |
| High1 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID12038In a retrospective study of 5,290 chronic lymphocytic leukemia (CLL) patients where chromosome-banding analysis (CBA) data was available, karyotype complexity was assessed for clinical impact. Karyoty… (full text at CIViC) PMID 30602617 · Baliakas et al., 2019 · Open in CIViC | civic |
| GNAS c.393T>C1 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Better Outcome | 4 | accepted | EID2897In a retrospective study of 144 patients with B-cell chronic lymphocytic leukemia, the median progression-free survival was significantly different between GNAS T393C genotypes (TT 130 months; TC 100 … (full text at CIViC) PMID 17020971 · Frey et al., 2006 · Open in CIViC | civic |
| MYD88 L265P1 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Better Outcome | 2 | accepted | EID1489MYD88 mutations were identified in 24 of 1080 screened CLLs. They were exclusively seen in instances of mutated IGHV genes (18/23, P = 0.0001), a widely recognized prognostic signature for better out… (full text at CIViC) PMID 24943832 · Baliakas et al., 2015 · Open in CIViC | civic |
| NOTCH1 Mutation3 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | A | Supports Poor Outcome | 5 | accepted | EID1538In a study of 406 previously untreated CLL cases, a multivariate analysis indicated clonal NOTCH1 mutations (N=55) were significantly associated with reduced overall survival (HR: 1.5; 95%CI: 1.13-1.9… (full text at CIViC) PMID 26837699 · Nadeu et al., 2016 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Does Not Support Poor Outcome | 5 | accepted | EID1486In a multivariate analysis of 774 CLL patients, NOTCH1 mutations were not significantly correlated with shorter time to first treatment (HR=1.305; 95% CI=0.923-1.847). PMID 24943832 · Baliakas et al., 2015 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 2 | accepted | ||
| NOTCH1 P2514FS2 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1014NOTCH1 mutations were found to be associated with worse overall survival (3.77-fold increase in the hazard of death, P < .001) in a series of 309 newly diagnosed CLL and confirmed in an additional set… (full text at CIViC) PMID 22077063 · Rossi et al., 2012 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID495In a cohort of 120 patients with chronic lymphoytic leukemia, those with P2515 frameshift deletions in NOTCH1 at diagnosis had worse overall and treatment free survival. NOTCH1 mutations were also fou… (full text at CIViC) PMID 21670202 · Fabbri et al., 2011 · Open in CIViC | civic |
| PLCG2 D1140E1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia | Predictive | C | Supports Resistance | 2 | submitted | EID10372The effective cohort in this study was 11 CLL patients who were first treated with ibrutinib and then on progression treated with venetoclax until progression. Patient samples were sequenced before an… (full text at CIViC) PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| PLCG2 MUTATION1 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID5834Whole exome sequencing was performed on baseline and relapse samples from six patients with CLL. One relapse sample had mutations in BTK and PLCG2, and a second relapse sample only had a mutation in … (full text at CIViC) PMID 24869598 · Woyach et al., 2014 · Open in CIViC | civic |
| PLCG2 N571S1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia | Predictive | C | Supports Resistance | 2 | submitted | EID10371The effective cohort in this study was 11 CLL patients who were first treated with ibrutinib and then on progression treated with venetoclax until progression. Patient samples were sequenced before an… (full text at CIViC) PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| POT1 MUTATION1 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID1590In previously untreated patients with chronic lymphocytic leukemia, POT1 mutations (N=13) were associated with shorter overall survival than wildtype POT1 (N=148) in univariate and multivariate analys… (full text at CIViC) PMID 27226433 · Herling et al., 2016 · Open in CIViC | civic |
| SF3B1 Mutation4 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | A | Supports Poor Outcome | 5 | accepted | EID1540In a study of 406 previously untreated CLL cases, a multivariate analysis indicated SF3B1 mutations (N=51) were significantly associated with reduced time to first treatment (HR: 1.73; 95%CI: 1.05-2.8… (full text at CIViC) PMID 26837699 · Nadeu et al., 2016 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID1487In a multivariate analysis of 774 CLL patients, SF3B1 mutations were significantly correlated with shorter time to first treatment (HR=1.644; 95% CI=1.134-2.383). This finding was independent of IGHV … (full text at CIViC) PMID 24943832 · Baliakas et al., 2015 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | ||||
| TP53 Mutation9 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | A | Supports Poor Outcome | 5 | accepted | EID1507In a cohort of 406 patients with CLL, those patients with clonal or sub-clonal mutations in TP53 had significantly shorter overall survival (HR: 1.71; 95% CI: 1.28-2.26; P = .0001). PMID 26837699 · Nadeu et al., 2016 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID1452The authors analyzed 328 patients with CLL, of which 28 were identified to have TP53 mutations. Patients with TP53 mutations were found to have significantly shorter progression-free (HR = 3.8; P < 0.… (full text at CIViC) PMID 20697090 · Zenz et al., 2010 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 5 | accepted | ||
Data updated 18 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.
EID1479In the randomized UK LRF CCL4 phase 3 trial comparing first-line treatment with chlorambucil, fludarabine, or fludarabine plus cyclophosphamide, univariate analysis of patients with NOTCH1 mutations (… (full text at CIViC) PMID 23086750 · Oscier et al., 2013 · Open in CIViC |
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| accepted |
EID510In patients with chronic lymphocytic leukemia, those with mutations in SF3B1 had shorter time to treatment, progression-free survival, and overall survival. A majority of the mutations are in the C-te… (full text at CIViC) PMID 23568491 · Wan et al., 2013 · Open in CIViC |
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| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1480In the randomized phase 3 UK LRF CCL4 trial comparing first-line treatment with chlorambucil, fludarabine, or fludarabine plus cyclophosphamide, SF3B1 mutations (73/437 patients) were associated with … (full text at CIViC) PMID 23086750 · Oscier et al., 2013 · Open in CIViC | civic |
EID1485In a multivariate analysis of 774 CLL patients, TP53 aberrations were significantly correlated with shorter time to first treatment (HR=2.081; 95% CI=1.431-3.021). This finding was independent of IGHV… (full text at CIViC) PMID 24943832 · Baliakas et al., 2015 · Open in CIViC |
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| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1451In a study of 126 patients with long-term follow-up, TP53 mutations were significantly associated with shorter median survival in patients (P = 0.002) from time of diagnosis. The median survival from … (full text at CIViC) PMID 18689542 · Zenz et al., 2008 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID1450A study of 53 patients with B-CLL found a significant resistance to chemotherapy and corresponding poor clinical outcomes among the 7 treated patients with p53 mutations compared to the 29 treated pat… (full text at CIViC) PMID 8241511 · el Rouby et al., 1993 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID1478In the CLL4 trial assessing first line treatment with chlorambucil or fludarabine with or without cyclophosphamide, patients with TP53 mutations experienced poorer overall response rates (27% vs 83%),… (full text at CIViC) PMID 21483000 · Gonzalez et al., 2011 · Open in CIViC | civic |
| Alemtuzumab | Chronic Lymphocytic Leukemia | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID1481Thirty-six patients with CLL were treated with alemtuzumab. Partial or complete response was achieved in 6 of 15 patients with p53 mutations, compared to 4 of 21 without. These findings are not statis… (full text at CIViC) PMID 14726385 · Lozanski et al., 2004 · Open in CIViC | civic |
| Venetoclax | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Predictive | B | Does Not Support Resistance | 2 | submitted | EID6074In patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, patients with deletion 17p and/or mutations in TP53 (N=24) were not more likely to have progressive dis… (full text at CIViC) PMID 28473407 · Anderson et al., 2017 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaALIAS | Predictive | B | Does Not Support Resistance | 2 | rejected | EID12076In patients with relapsed /refractory chronic lymphocytes leukemia or small lymphocytic lymphoma, patients with deletion 17p and/or mutations in TP53 (N=24) were not more likely to have progressive di… (full text at CIViC) PMID 28473407 · Anderson et al., 2017 · Open in CIViC | civic |