title: The role of ATM mutations and 11q deletions in disease progression in chronic lymphocytic leukemia.
abstract: Abstract ATM gene alteration is a frequent event in pathogenesis of chronic lymphocytic leukemia (CLL) and occurs as monoallelic loss in the form of 11q23 deletion, with and without mutation in the remaining ATM allele. ATM is a principal DNA damage response gene and biallelic ATM alterations lead to ATM functional loss and chemoresistance. The introduction of new therapies, such as intensive chemoimmunotherapy and inhibition of B-cell receptor (BCR) signaling, has changed clinical responses for the majority of CLL tumors including those with 11q deletion, but it remains to be determined whether these strategies can prevent clonal evolution of tumors with biallelic ATM alterations. In this review we discuss ATM function and the consequences of its loss during CLL pathogenesis, differences in clinical behavior of tumors with monoallelic and biallelic ATM alterations, and we outline possible approaches for targeting the ATM null CLL phenotype.
authors.affiliation: School of Cancer Sciences, University of Birmingham , Birmingham , UK.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stankovic
authors.forename: Anna
authors.initials: A
authors.lastname: Skowronska
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D060965:Clonal Evolution; D018450:Disease Progression; D006801:Humans; D054868:Jacobsen Distal 11q Deletion Syndrome / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D058990:Molecular Targeted Therapy; D009154:Mutation; D010641:Phenotype; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: 11q deletion; ATM mutations; CLL; prognosis