title: Progressive but previously untreated CLL patients with greater array CGH complexity exhibit a less durable response to chemoimmunotherapy.
abstract: To better understand the implications of genomic instability and outcome in B-cell chronic lymphocytic leukemia (CLL), we sought to address genomic complexity as a predictor of chemosensitivity and ultimately clinical outcome in this disease. We used array-based comparative genomic hybridization (aCGH) with a one-million probe array and identified gains and losses of genetic material in 48 patients treated on a chemoimmunotherapy clinical trial. We identified chromosomal gain or loss in ≥6% of the patients on chromosomes 3, 8, 9, 10, 11, 12, 13, 14, and 17. Higher genomic complexity, as a mechanism favoring clonal selection, was associated with shorter progression-free survival, and predicted a poor response to treatment. Of interest, CLL cases with loss of p53 surveillance showed more complex genomic features and were found both in patients with a 17p13.1 deletion and in the more favorable genetic subtype characterized by the presence of 13q14.1 deletion. This aCGH study adds information on the association between poor trial response and increasing genetic complexity as CLL progresses.
authors.affiliation: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. kay.neil@mayo.edu
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.forename: Esteban
authors.initials: E
authors.lastname: Braggio
authors.forename: Scott
authors.initials: S
authors.lastname: Vanwier
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Van Dyke
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: Renee C
authors.initials: RC
authors.lastname: Tschumper
authors.forename: Thomas
authors.initials: T
authors.lastname: Kipps
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D004358:Drug Therapy / Q000379:methods; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents