Mutations in chronic lymphocytic leukemia and how they affect therapy choice: Focus on NOTCH1, SF3B1, and TP53

Clive S. Zent, W. Richard Burack

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by a relatively small number of recurrent genetic defects. These can be evaluated by clinically available methods such as fluorescent in situ hybridization and targeted sequencing approaches to provide data that can be very helpful in prognostication and planning of treatment. Acquired defects in the p53 pathway, activating mutations of NOTCH1, and dysfunctional mutations of SF3B1 and BIRC3 identify patients with higher risk of progressive disease, poorer responses to conventional chemoimmunotherapy, and shorter survival. Risk stratification using these data can identify patients with aggressive CLL who require careful monitoring and are unlikely to have durable responses to chemoimmunotherapy at disease progression. Patients with defective DNA damage repair mechanisms because of p53 dysfunction should be considered for non-chemotherapy-based regimens including tyrosine kinase inhibitors, BCL2 inhibitors, monoclonal antibodies, and immunological therapies including allogeneic transplantation and chimeric antigen receptor-targeted T cells. Conversely, patients with no high-risk mutations can usually be monitored for a prolonged time and are likely to have durable responses to chemoimmunotherapy at disease progression. New technologies for genetic analysis such as targeted next-generation sequencing have the potential to make these analyses cheaper, faster, and more widely available. Comprehensive genetic analysis of patients both at diagnosis and before treatment for progressive disease could become an integral component of care for CLL.

Original languageEnglish (US)
Pages (from-to)119-124
Number of pages6
JournalHematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
Volume2014
Issue number1
DOIs
StatePublished - Dec 5 2014
Externally publishedYes

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B-Cell Chronic Lymphocytic Leukemia
Mutation
Disease Progression
Therapeutics
Antigen Receptors
Histocompatibility Antigens
Homologous Transplantation
Fluorescence In Situ Hybridization
DNA Repair
Protein-Tyrosine Kinases
DNA Damage
Monoclonal Antibodies
Technology
T-Lymphocytes
Survival

ASJC Scopus subject areas

  • Hematology

Cite this

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