title: Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era.
abstract: OBJECTIVE
  Next-generation sequencing has identified new genetic markers that have altered prognosis for patients with chronic lymphocytic leukemia (CLL) at diagnosis. Understanding the significance of these prognostic indicators and recognizing their potential impact on treatment selection and patients' outcomes is critical for clinicians and investigators.
  
  
  OBJECTIVE
  To review novel prognostic factors at CLL diagnosis that have shown an impact on the prognosis and outcomes of this disease.
  
  
  METHODS
  Literature from January 2004 through December 2014 was searched in PubMed, Cochrane Central Register of Controlled Trials, and Scopus to identify English-language, peer-reviewed articles on clinical and prognostic factors for CLL (TP53, ATM, NOTCH1, SF3B1, BIRC3, and MYD88). Reference lists were subsequently reviewed for additional articles. A total of 450 articles was identified, and 48 articles meeting inclusion criteria were reviewed.
  
  
  RESULTS
  Among prognostic markers reviewed, chromosomal aberrations have been validated and are currently used clinically to predict prognosis. Patients with 17p13.1 deletion have poor response to chemoimmunotherapy and are treated differently, with some undergoing allogeneic transplantation in first remission. CD38 and ZAP-70 status of malignant cells and unmutated immunoglobulin variable heavy chain gene have similarly been validated to predict adverse prognosis, but their implications on treatment selection have not been proven. The presence of TP53 and ATM mutations predicts worse prognosis, which has been corroborated in various studies. Patients with TP53 mutations have lower responses to chemoimmunotherapy. Furthermore, patients with TP53 and ATM mutations have inferior progression-free survival and overall survival, independent of other factors. Patients carrying the NOTCH1 and SF3B1 mutations have worse prognosis; patients with the NOTCH1 mutation have lower response rates to standard chemoimmunotherapy. The impact of BIRC3 on prognosis and survival requires further confirmation.
  
  
  CONCLUSIONS
  The heterogeneous clinical course of CLL is likely explained by underlying molecular prognostic factors. Moving forward, analyzing these factors at diagnosis is recommended for better prognostication.
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois2Section of Hematology/Oncology, Cancer Cytogenetics Laboratory, University of Chicago, Chicago, Illinois.
authors.forename: Gordana
authors.initials: G
authors.lastname: Raca
authors.affiliation: Division of Genomic and Molecular Pathology, Department of Pathology, University of Chicago, Chicago, Illinois.
authors.forename: Y Lynn
authors.initials: YL
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D058990:Molecular Targeted Therapy; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor