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. 2022 Feb 1;97(2):E47-E51.
doi: 10.1002/ajh.26411. Epub 2021 Nov 24.

Identification of recurrent genomic alterations in the apoptotic machinery in chronic lymphocytic leukemia patients treated with venetoclax monotherapy

Relja Popovic  1 , Fengjiao Dunbar  1 , Charles Lu  1 , Kenneth Robinson  1 , Danjuma Quarless  1 , Scott E Warder  1 , Nabanita Mukherjee  1 , John Pesko  1 , Andrew J Souers  1 , Jeffrey F Waring  1 , Matthew S Davids  2 , Eugen Tausch  3 , Stephan Stilgenbauer  3 , Jeremy A Ross  1 , Joel D Leverson  1 , Su Young Kim  1 , Brenda J Chyla  1
Affiliations

Identification of recurrent genomic alterations in the apoptotic machinery in chronic lymphocytic leukemia patients treated with venetoclax monotherapy

Relja Popovic et al. Am J Hematol. .
No abstract available

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Conflict of interest statement

R.P., F.D., C.L., K.R., D.Q., S.E.W., N.M., A.J.S., J.F.W., J.A.R., and B.J.C. are employees of AbbVie and may hold stock or other options; J.P. is a former employee of AbbVie, current employee of GlaxoSmithKline, and may hold stock or other options with AbbVie; M.S.D. received institutional research grants from AbbVie, Ascentage Pharma, AstraZeneca, Genentech, MEI Pharma, Novartis, Surface Oncology, TG Therapeutics, and Verastem; and personal fees from AbbVie, Adaptive Biotechnologies, Ascentage Pharma, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, MEI Pharma, Merck, Novartis, Research to Practice, Takeda, TG Therapeutics, and Verastem; E.T. received fees for consulting and research support from AbbVie, Janssen, and Roche; S.S. received fees for consulting, drug/equipment, funding, and writing assistance from AbbVie, AstraZeneca, Celgene, Gilead, GlaxoSmithKline, Hoffman La‐Roche, Janssen, Novartis, Pharmacyclics, and Sunesis; J.D.L. is a former employee of AbbVie, current employee of Pfizer, and may hold stock or other options with AbbVie; S.Y.K. is a former employee of AbbVie, current employee of Nurix Therapeutics, and may hold stock or other options with AbbVie.

Figures

FIGURE 1
FIGURE 1
(A) Gene deletions identified from a pooled genome‐wide CRISPR screen in SU‐DHL4 cells that confer venetoclax resistance. (B) Tumor genomic changes in patients with CLL after venetoclax monotherapy. (C) Acquired mutations in apoptotic machinery after venetoclax monotherapy. (D) Frequency of acquired mutations after venetoclax monotherapy. (E) Acquired BCL2 mutations after venetoclax monotherapy. (F) Variant allele frequency of mutations. (G) Upregulation of genes in patients who relapsed on venetoclax monotherapy. (H) Changes in expression of BCL2 family genes pre‐ and post‐treatment. * represents significant expression changes (FDR < 0.05). CR, complete remission; CRi, complete remission with incomplete hematopoietic recovery; nPR, nodular partial remission; NR, nonresponder; PR, partial remission; VAF, variant allele frequency
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