TY - JOUR
T1 - Progressive but previously untreated CLL patients with greater array CGH complexity exhibit a less durable response to chemoimmunotherapy
AU - Kay, Neil E.
AU - Eckel-Passow, Jeanette E.
AU - Braggio, Esteban
AU - VanWier, Scott
AU - Shanafelt, Tait D.
AU - Van Dyke, Daniel L.
AU - Jelinek, Diane F.
AU - Tschumper, Renee C.
AU - Kipps, Thomas
AU - Byrd, John C.
AU - Fonseca, Rafael
N1 - Funding Information:
This manuscript was supported in part by grants from the NIH/NCI ( CA81534 awarded to T.K.; CA95241 awarded to N.E.K.; and CA136591 awarded to D.F.J.) and philanthropic support from Edson Spencer and the Donner Foundations . Rafael Fonseca is a clinical investigator of the Damon Runyon Cancer Research Fund. This work is supported by grants SPORE CA90297052 , P01 CA62242 , R01 CA83724 , ECOG CA 21115T , Predolin Foundation , Mayo Clinic Cancer Center , and the Mayo Foundation . We would like to acknowledge the statistical support provided by Ruchi Sharma.
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cancergencyto.2010.09.003
DO - 10.1016/j.cancergencyto.2010.09.003
M3 - Article
C2 - 21156228
AN - SCOPUS:78650010643
SN - 0165-4608
VL - 203
SP - 161
EP - 168
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
IS - 2
ER -