Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2019 Sep;104(9):e434-e437.
doi: 10.3324/haematol.2019.222588. Epub 2019 Apr 19.

Venetoclax resistance and acquired BCL2 mutations in chronic lymphocytic leukemia

Eugen Tausch  1 , William Close  1 , Anna Dolnik  2 , Johannes Bloehdorn  1 , Brenda Chyla  3 , Lars Bullinger  2 , Hartmut Döhner  1 , Daniel Mertens  1   4 , Stephan Stilgenbauer  5   6
Affiliations
Case Reports

Venetoclax resistance and acquired BCL2 mutations in chronic lymphocytic leukemia

Eugen Tausch et al. Haematologica. 2019 Sep.
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
History of an exemplary patient that acquired a BCL2 G101V mutation during treatment with venetoclax. A. Timeline of patient treatment (yellow bars) and sample collection time points (orange arrows). Variant allelic fraction (VAF) of G101V BCL2 in different samples measured via WES. Targeted NGS was used to confirm the presence (✓) or absence (✘) of the variant. B. Prevalence of all mutations found in the spleen (red) and bone marrow (blue) at relapse, but not at baseline. Mutations are sorted based on the mean VAF of the spleen and bone marrow samples.
Figure 2.
Figure 2.
Treatment course and appearance of BCL2 mutations in three CLL patients. Relative lymphocyte count (LC%, blue), white blood count (WBC, black) and platelets (PLT, green) are shown for 3 different CLL patients from the initiation of the treatment with venetoclax to progression. Variants in BCL2 are shown for different time points and in different tissues are shown (PB=peripheral blood, BM=bone marrow, SP=spleen). G101V is depicted in blue, D103Y in red. The VAF is estimated from targeted sequencing (except for bone marrow sample 2 of patient 1 [BM*], in which it is estimated from WES).
Figure 3.
Figure 3.
A. Surface model of BCL2 (grey) with areas in close contact to venetoclax in green and residues V148 and F104 highlighted in cyan. B. Surface model of A) with superimposed D103Y point mutation (red) showing three different conformational states. C. BCL2 ribbon structure (green), superimposed G101V point mutation (red) and close neighboring amino acids (cyan) with distances indicated. The crystal structure was obtained and modified from PDB:4MAN.
See this image and copyright information in PMC

Comment in

References

    1. Kater AP, Seymour JF, Hillmen P, et al. Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study. J Clin Oncol. 2019;37(4):4:269–277. - PubMed
    1. Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016;374(4):311–322. - PMC - PubMed
    1. Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018;378(12):1107–1120. - PubMed
    1. Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial. J Clin Oncol. 2018;36(19):1973–1980. - PubMed
    1. Blombery P, Anderson MA, Gong J, et al. Acquisition of the recurrent Gly101Val mutation in BCL2 confers resistance to venetoclax in patients with progressive chronic lymphocytic leukemia. Cancer Discov. 2018;9(3):342–353. - PubMed

Publication types

MeSH terms