title: Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics.
abstract: Approximately 45% of adults with acute myeloid leukemia (AML) have normal cytogenetics and therefore lack structural abnormalities that can assist in the localization and characterization of molecular defects. The partial tandem duplication of the ALL1 (MLL) gene has been found in several such cases of AML, yet its frequency and clinical significance are unclear. We performed Southern analysis of the ALL1 gene in pretreatment samples from 98 AML patients with normal cytogenetics. Eleven of 98 such patients (11%; 95% confidence interval, 6-19%) showed rearrangement of ALL1 at diagnosis. The partial tandem duplication of ALL1 was responsible for ALL1 rearrangement in all such cases examined, making it a frequent molecular defect in adult AML patients with normal cytogenetics. Furthermore, patients with ALL1 rearrangement had a significantly shorter duration of complete remission when compared to patients without ALL1 rearrangement (P = 0.01; median, 7.1 versus 23.2 months). This defect defines for the first time a subset of AML patients with normal cytogenetics who have short durations of complete remission and thus require new therapeutic approaches.
authors.affiliation: Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: M P
authors.initials: MP
authors.lastname: Strout
authors.forename: D
authors.initials: D
authors.lastname: Lawrence
authors.forename: D C
authors.initials: DC
authors.lastname: Arthur
authors.forename: M R
authors.initials: MR
authors.lastname: Baer
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.forename: S
authors.initials: S
authors.lastname: Knuutila
authors.forename: K
authors.initials: K
authors.lastname: Mrózek
authors.forename: A R
authors.initials: AR
authors.lastname: Oberkircher
authors.forename: G
authors.initials: G
authors.lastname: Marcucci
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: E
authors.initials: E
authors.lastname: Elonen
authors.forename: A W
authors.initials: AW
authors.lastname: Block
authors.forename: P N
authors.initials: PN
authors.lastname: Rao
authors.forename: G P
authors.initials: GP
authors.lastname: Herzig
authors.forename: B L
authors.initials: BL
authors.lastname: Powell
authors.forename: T
authors.initials: T
authors.lastname: Ruutu
authors.forename: C A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D005260:Female; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged