BCL2

Predictive

Supports Resistance

submitted

EID8311

This study is a follow-up report after the original publication (PMID 30514704). D103E mutation was identified in combination with other BCL2 mutations including G101V in 4 CLL patients with venetocla… (full text at CIViC)

PMID 31951646 · Blombery et al., 2020 · Open in CIViC

〃

Predictive

Supports Resistance

submitted

EID8335

The authors demonstrated that BCL2 Asp103Glu imparts resistance to venetoclax in vitro by investigating the in vitro binding profile of the Asp103Glu to both venetoclax and proapoptotic proteins in co… (full text at CIViC)

PMID 31951646 · Blombery et al., 2020 · Open in CIViC

BCL2 D103V1
Venetoclax	Chronic Lymphocytic Leukemia	Predictive	C	Supports Resistance	3	submitted	EID8310 This study is a follow-up report after the original publication (PMID 30514704). D103V mutation was identified in combination with other BCL2 mutations including G101V in 2 CLL patients with venetocla… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC	civic

BCL2 D103V1

Predictive

Supports Resistance

submitted

EID8310

This study is a follow-up report after the original publication (PMID 30514704). D103V mutation was identified in combination with other BCL2 mutations including G101V in 2 CLL patients with venetocla… (full text at CIViC)

PMID 31951646 · Blombery et al., 2020 · Open in CIViC

BCL2 D103Y2
Venetoclax	Chronic Lymphocytic Leukemia	Predictive	B	Supports Resistance	4	submitted	EID8312 This study is a follow-up report after the original publication (PMID 30514704). D103Y mutation was identified in combination with other BCL2 mutations including G101V in 5 CLL patients with venetocla… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC	civic
〃	Chronic Lymphocytic Leukemia	Predictive	C	Supports Resistance	2	submitted	EID8304 This study identified D103Y in one CLL patient with resistance to venetoclax. D103Y was presented in this patient after 39 months of venetoclax treatment in peripheral blood with a VAF of 7% which inc… (full text at CIViC) PMID 31004028 · Tausch et al., 2019 · Open in CIViC	civic

BCL2 D103Y2

Predictive

Supports Resistance

submitted

EID8312

This study is a follow-up report after the original publication (PMID 30514704). D103Y mutation was identified in combination with other BCL2 mutations including G101V in 5 CLL patients with venetocla… (full text at CIViC)

PMID 31951646 · Blombery et al., 2020 · Open in CIViC

〃

Predictive

Supports Resistance

submitted

EID8304

This study identified D103Y in one CLL patient with resistance to venetoclax. D103Y was presented in this patient after 39 months of venetoclax treatment in peripheral blood with a VAF of 7% which inc… (full text at CIViC)

PMID 31004028 · Tausch et al., 2019 · Open in CIViC

BCL2 F104I2
Venetoclax	Follicular Lymphoma	Predictive	C	Supports Resistance	2	accepted	EID8375 This study identified BCL2 F104I mutation in one Follicular Lymphoma patient who developed resistance to venetoclax. Codon 104 is located at the venetoclax binding site of BCL2. PMID 31234236 · Blombery et al., 2019 · Open in CIViC	civic
〃	Follicular Lymphoma	Predictive	D	Supports Resistance	3	accepted	EID8376 Rs4;11 cells overexpressing BCL2 F104I exhibited >40-fold greater resistance to venetoclax after 24-hour treatment (IC50 not reached) than Rs4;11 overexpressing BCL2 WT cells as determined by cell tit… (full text at CIViC) PMID 31234236 · Blombery et al., 2019 · Open in CIViC	civic

BCL2 F104I2

Predictive

Supports Resistance

accepted

EID8375

This study identified BCL2 F104I mutation in one Follicular Lymphoma patient who developed resistance to venetoclax. Codon 104 is located at the venetoclax binding site of BCL2.

PMID 31234236 · Blombery et al., 2019 · Open in CIViC

〃

Predictive

Supports Resistance

accepted

EID8376

Rs4;11 cells overexpressing BCL2 F104I exhibited >40-fold greater resistance to venetoclax after 24-hour treatment (IC50 not reached) than Rs4;11 overexpressing BCL2 WT cells as determined by cell tit… (full text at CIViC)

PMID 31234236 · Blombery et al., 2019 · Open in CIViC

BCL2 F104L1
Venetoclax	Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Predictive	B	Supports Resistance	3	submitted	EID8187 Associated with venetoclax resistance in 2 high-risk CLL patients post ibrutinib in "progressive CLL" PMID 32232486 · Lucas et al., 2020 · Open in CIViC	civic

BCL2 F104L1

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Predictive

Supports Resistance

submitted

EID8187

Associated with venetoclax resistance in 2 high-risk CLL patients post ibrutinib in "progressive CLL"

PMID 32232486 · Lucas et al., 2020 · Open in CIViC

BCL2 F104S1
Venetoclax	Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Predictive	B	Supports Resistance	3	submitted	EID8186 Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL" PMID 32232486 · Lucas et al., 2020 · Open in CIViC	civic

BCL2 F104S1

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Predictive

Supports Resistance

submitted

EID8186

Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL"

PMID 32232486 · Lucas et al., 2020 · Open in CIViC

BCL2 G101A1
Venetoclax	Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Predictive	B	Supports Resistance	4	submitted	EID8184 Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL" PMID 32232486 · Lucas et al., 2020 · Open in CIViC	civic

BCL2 G101A1

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Predictive

Supports Resistance

submitted

EID8184

Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL"

PMID 32232486 · Lucas et al., 2020 · Open in CIViC

BCL2 G101V7
Venetoclax	Chronic Lymphocytic Leukemia	Predictive	B	Supports Resistance	4	submitted	EID8174 This study identified G101V mutation in BCL2 emerged in 7 out of 15 patients with CLL progression treated with Venetoclax. In addition, this study demonstrated that the G101V mutation impairs binding … (full text at CIViC) PMID 30514704 · Blombery et al., 2019 · Open in CIViC	civic
〃	Chronic Lymphocytic Leukemia	Predictive	C	Supports Resistance	4	submitted	EID7970 Four of six heavily pretreated, high-risk CLL patients with a 17p deletion from the phase 2 trial M13-9824 with continuous venetoclax treatment, who were treated with venetoclax for a period longer th… (full text at CIViC) PMID 31004028 · Tausch et al., 2019 · Open in CIViC	civic
〃	Chronic Lymphocytic Leukemia	Predictive	C	Supports Resistance	4	submitted	EID8305 This study is a follow-up report after the original publication (PMID 30514704). The authors described multiple acquired resistance mutations including G101V in BCL-2 that occur in different CLL cells… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC	civic
〃	Chronic Lymphocytic Leukemia	Predictive	C	Does Not Support Resistance	3	submitted	EID8303 Previous work by this group used WES and was unable to identify BCL2 G101V mutation in 9 CLL patients with resistance to venetoclax (PMID 29463802). Based on Tausch et al work (PMID 31004028), this gr… (full text at CIViC) PMID 31666345 · Weiss et al., 2019 · Open in CIViC	civic
〃	Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Predictive	C	Supports Resistance	2	accepted	EID8185 The 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
〃	Chronic Lymphocytic Leukemia	Predictive	D	Supports Resistance	3	submitted	EID8334 This study demonstrated that the G101V mutation impairs binding of venetoclax to BCL2, confers resistance to venetoclax in both patient leukemia cells and engineered cell lines, thus provides a select… (full text at CIViC) PMID 30514704 · Blombery et al., 2019 · Open in CIViC	civic
〃	Chronic Lymphocytic Leukemia	Predictive	D	Supports Resistance	3	accepted	EID8841 This study described the similar crystal structures of BCL-2 wild-type and G101V when bound to venetoclax. Steady state competition surface plasmon resonance experiments demonstrated a ~177 fold decre… (full text at CIViC) PMID 31160589 · Birkinshaw et al., 2019 · Open in CIViC	civic

BCL2 G101V7

Predictive

Supports Resistance

submitted

EID8174

This study identified G101V mutation in BCL2 emerged in 7 out of 15 patients with CLL progression treated with Venetoclax. In addition, this study demonstrated that the G101V mutation impairs binding … (full text at CIViC)

PMID 30514704 · Blombery et al., 2019 · Open in CIViC

〃

Predictive

Supports Resistance

submitted

EID7970

Four of six heavily pretreated, high-risk CLL patients with a 17p deletion from the phase 2 trial M13-9824 with continuous venetoclax treatment, who were treated with venetoclax for a period longer th… (full text at CIViC)

PMID 31004028 · Tausch et al., 2019 · Open in CIViC

〃

Predictive

Supports Resistance

submitted

EID8305

This study is a follow-up report after the original publication (PMID 30514704). The authors described multiple acquired resistance mutations including G101V in BCL-2 that occur in different CLL cells… (full text at CIViC)

PMID 31951646 · Blombery et al., 2020 · Open in CIViC

〃

Predictive

Does Not Support Resistance

submitted

EID8303

Previous work by this group used WES and was unable to identify BCL2 G101V mutation in 9 CLL patients with resistance to venetoclax (PMID 29463802). Based on Tausch et al work (PMID 31004028), this gr… (full text at CIViC)

PMID 31666345 · Weiss et al., 2019 · Open in CIViC

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

〃

Predictive

Supports Resistance

accepted

EID8185

The 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

〃

Predictive

Supports Resistance

submitted

EID8334

This study demonstrated that the G101V mutation impairs binding of venetoclax to BCL2, confers resistance to venetoclax in both patient leukemia cells and engineered cell lines, thus provides a select… (full text at CIViC)

PMID 30514704 · Blombery et al., 2019 · Open in CIViC

〃

Predictive

Supports Resistance

accepted

EID8841

This study described the similar crystal structures of BCL-2 wild-type and G101V when bound to venetoclax. Steady state competition surface plasmon resonance experiments demonstrated a ~177 fold decre… (full text at CIViC)

PMID 31160589 · Birkinshaw et al., 2019 · Open in CIViC

BCL2 L119V1
Venetoclax	Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Predictive	B	Supports Resistance	3	submitted	EID8190 Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL" PMID 32232486 · Lucas et al., 2020 · Open in CIViC	civic

BCL2 L119V1

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Predictive

Supports Resistance

submitted

EID8190

Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL"

PMID 32232486 · Lucas et al., 2020 · Open in CIViC

BCL2 Mutation1
(prognostic)	Follicular Lymphoma	Prognostic	B	Supports Poor Outcome	3	accepted	EID5992 In a multivariate analysis, BCL2 mutations and high FL international prognostic index were independent risk factors for transformation and death due to lymphoma. Some mutant Bcl-2 proteins exhibited e… (full text at CIViC) PMID 25452615 · Correia et al., 2015 · Open in CIViC	civic

BCL2 Mutation1

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID5992

In a multivariate analysis, BCL2 mutations and high FL international prognostic index were independent risk factors for transformation and death due to lymphoma. Some mutant Bcl-2 proteins exhibited e… (full text at CIViC)

PMID 25452615 · Correia et al., 2015 · Open in CIViC

BCL2 Overexpression3
(prognostic)	Diffuse Large B-Cell LymphomaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	4	accepted	EID423 In patients with Diffuse Large B-Cell Lymphoma, those with increased levels of BCL2 were shown to have decreased overall, disease-free, and relapse-free survival. PMID 9207459 · Gascoyne et al., 1997 · Open in CIViC	civic
〃	Diffuse Large B-Cell LymphomaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	4	rejected	EID424 In patients with Diffuse Large B-Cell Lymphoma, those with increased levels of BCL2 were shown to have decreased OS, DFS, and RFS. PMID 9207459 · Gascoyne et al., 1997 · Open in CIViC	civic
Dinaciclib + VenetoclaxCombination	Lymphoma	Predictive	D	Supports Resistance	2	submitted	EID9313 Within a preclinical study, the efficacy of Dinaciclib and ABT-199 in MYC-BCL2 double expressing lymphoma (DLBCL) was investigated through mouse models and DLBCL cell lines. Overexpressing DLBCL BCL2 … (full text at CIViC) PMID 25882699 · Li et al., 2015 · Open in CIViC	civic

BCL2 Overexpression3

(prognostic)

Diffuse Large B-Cell LymphomaCURATED_BROADER

Prognostic

Supports Poor Outcome

accepted

EID423

In patients with Diffuse Large B-Cell Lymphoma, those with increased levels of BCL2 were shown to have decreased overall, disease-free, and relapse-free survival.

PMID 9207459 · Gascoyne et al., 1997 · Open in CIViC

〃

Diffuse Large B-Cell LymphomaCURATED_BROADER

Prognostic

Supports Poor Outcome

rejected

EID424

In patients with Diffuse Large B-Cell Lymphoma, those with increased levels of BCL2 were shown to have decreased OS, DFS, and RFS.

PMID 9207459 · Gascoyne et al., 1997 · Open in CIViC

Dinaciclib + VenetoclaxCombination

Lymphoma

Predictive

Supports Resistance

submitted

EID9313

Within a preclinical study, the efficacy of Dinaciclib and ABT-199 in MYC-BCL2 double expressing lymphoma (DLBCL) was investigated through mouse models and DLBCL cell lines. Overexpressing DLBCL BCL2 … (full text at CIViC)

PMID 25882699 · Li et al., 2015 · Open in CIViC

BCL2 R107_R110dup2
Venetoclax	Chronic Lymphocytic Leukemia	Predictive	B	Supports Resistance	4	submitted	EID8309 This study is a follow-up report after the original publication (PMID 30514704). R107_R110dup mutation was identified in combination with other BCL2 mutations including G101V in 5 CLL patients with ve… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC	civic
〃	Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Predictive	B	Supports Resistance	3	submitted	EID8188 Associated with venetoclax resistance in high-risk CLL patients post ibrutinib in 2 cases of "progressive CLL" and 1 case of Richter transformation PMID 32232486 · Lucas et al., 2020 · Open in CIViC	civic

BCL2 R107_R110dup2

Predictive

Supports Resistance

submitted

EID8309

This study is a follow-up report after the original publication (PMID 30514704). R107_R110dup mutation was identified in combination with other BCL2 mutations including G101V in 5 CLL patients with ve… (full text at CIViC)

PMID 31951646 · Blombery et al., 2020 · Open in CIViC

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

〃

Predictive

Supports Resistance

submitted

EID8188

Associated with venetoclax resistance in high-risk CLL patients post ibrutinib in 2 cases of "progressive CLL" and 1 case of Richter transformation

PMID 32232486 · Lucas et al., 2020 · Open in CIViC

BCL2 R129L1
Venetoclax	Chronic Lymphocytic Leukemia	Predictive	C	Supports Resistance	3	submitted	EID8307 This study is a follow-up report after the original publication (PMID 30514704). R129L mutation was identified in combination with other BCL2 mutations including G101V in 2 CLL patients with venetocla… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC	civic

BCL2 R129L1

Predictive

Supports Resistance

submitted

EID8307

This study is a follow-up report after the original publication (PMID 30514704). R129L mutation was identified in combination with other BCL2 mutations including G101V in 2 CLL patients with venetocla… (full text at CIViC)

PMID 31951646 · Blombery et al., 2020 · Open in CIViC

BCL2 reg_e@[IGH]::BCL22
(diagnostic)	Follicular Lymphoma	Diagnostic	B	Supports Positive	5	submitted	EID11808 This translocation is a hallmark feature of follicular lymphoma. Although it is not present in every case, it is one of the most common genetic features of FL. FISH or IHC staining for BCL2 is part of… (full text at CIViC) PMID 3537802 · Yunis et al., 1987 · Open in CIViC	civic
〃	Diffuse Large B-Cell LymphomaCURATED_BROADER	Diagnostic	B	Supports Positive	4	accepted	EID407 The t(14;18) transloaction of BCL2 is shown to be associated with germinal-center B-cell–like diffuse large-B-cell lymphomas. PMID 12075054 · Rosenwald et al., 2002 · Open in CIViC	civic

BCL2 reg_e@[IGH]::BCL22

(diagnostic)

Diagnostic

Supports Positive

submitted

EID11808

This translocation is a hallmark feature of follicular lymphoma. Although it is not present in every case, it is one of the most common genetic features of FL. FISH or IHC staining for BCL2 is part of… (full text at CIViC)

PMID 3537802 · Yunis et al., 1987 · Open in CIViC

〃

Diffuse Large B-Cell LymphomaCURATED_BROADER

Diagnostic

Supports Positive

accepted

EID407

The t(14;18) transloaction of BCL2 is shown to be associated with germinal-center B-cell–like diffuse large-B-cell lymphomas.

PMID 12075054 · Rosenwald et al., 2002 · Open in CIViC

High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements

BCL2 Translocation1
(diagnostic)	High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements	Diagnostic	A	Supports Positive	4	submitted	EID11810 The combination of these genetic features are diagnostic for this newly defined entity as per the latest ICC and WHO guidelines PMID 35653592 · Campo et al., 2022 · Open in CIViC	civic

BCL2 Translocation1

(diagnostic)

Diagnostic

Supports Positive

submitted

EID11810

The combination of these genetic features are diagnostic for this newly defined entity as per the latest ICC and WHO guidelines

PMID 35653592 · Campo et al., 2022 · Open in CIViC

BCL2 V156D1
Venetoclax	Chronic Lymphocytic Leukemia	Predictive	B	Supports Resistance	4	submitted	EID8306 This study is a follow-up report after the original publication (PMID 30514704). V156D mutation was identified in combination with other BCL2 mutations including G101V in 6 CLL patients with venetocla… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC	civic

BCL2 V156D1

Predictive

Supports Resistance

submitted

EID8306

This study is a follow-up report after the original publication (PMID 30514704). V156D mutation was identified in combination with other BCL2 mutations including G101V in 6 CLL patients with venetocla… (full text at CIViC)

PMID 31951646 · Blombery et al., 2020 · Open in CIViC

High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements

BCL2 Translocation + MYC TranslocationMYC BCL21
(diagnostic)	High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements	Diagnostic	A	Supports Positive	4	submitted	EID11811 MYC and BCL2 rearrangements together are defining diagnostic features of this new entity PMID 35653592 · Campo et al., 2022 · Open in CIViC	civic

BCL2 Translocation + MYC TranslocationMYC BCL21

(diagnostic)

Diagnostic

Supports Positive

submitted

EID11811

MYC and BCL2 rearrangements together are defining diagnostic features of this new entity

PMID 35653592 · Campo et al., 2022 · Open in CIViC

BCL2 Translocation + BCL6 Translocation + MYC TranslocationMYC BCL2 BCL61
(prognostic)	Diffuse Large B-Cell LymphomaCURATED_BROADER	Prognostic	C	Supports Poor Outcome	2	submitted	EID9813 In 2016 the WHO added a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with MYC AND [BCL2 OR BCL6] translocations. These represent less than 1… (full text at CIViC) PMID 28600333 · Friedberg, 2017 · Open in CIViC	civic

BCL2 Translocation + BCL6 Translocation + MYC TranslocationMYC BCL2 BCL61

(prognostic)

Diffuse Large B-Cell LymphomaCURATED_BROADER

Prognostic

Supports Poor Outcome

submitted

EID9813

In 2016 the WHO added a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with MYC AND [BCL2 OR BCL6] translocations. These represent less than 1… (full text at CIViC)

PMID 28600333 · Friedberg, 2017 · Open in CIViC