title: AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features.
abstract: Balanced chromosomal rearrangements define distinct entities in acute myeloid leukemia (AML). Here, we present 13 AML cases with t(8;16)(p11;p13) with observed low incidence (13/6124 patients), but more frequent presentation in therapy-related AML than in de novo AML (7/438 versus 6/5686, P=0.00001). Prognosis was poor with median overall survival of 4.7 months. Cytomorphology was characterized by parallel positive myeloperoxidase and non-specific esterase staining, therefore, French-American-British (FAB)-classification was impossible and origin of the AML with t(8;16) from an early stem cell with myeloid and monoblastic potential is hypothesized. Erythrophagocytosis was observed in 7/13 cases. Using gene expression profiling on 407 cases, patients with t(8;16) were compared to AML FAB subtypes with normal karyotype. Principal component analyses demonstrated that AML with t(8;16) were distinct from FAB subtypes M1, M4, M5a/b. When further compared to AML showing balanced rearrangements, that is, current WHO categories t(15;17), t(8;21), inv(16) and t(11q23)/MLL, AML with t(8;16) cases were clustered close to t(11q23)/MLL sharing commonly expressed genes. Subsequently, a pairwise comparison discriminated AML with t(8;16) from AML with t(11q23)/MLL, thus defining a highly unique signature for AML with t(8;16). In conclusion, AML with t(8;16) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features and is a specific subtype of AML.
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany. torsten.haferlach@mll-online.com
authors.forename: T
authors.initials: T
authors.lastname: Haferlach
authors.forename: A
authors.initials: A
authors.lastname: Kohlmann
authors.forename: H-U
authors.initials: HU
authors.lastname: Klein
authors.forename: C
authors.initials: C
authors.lastname: Ruckert
authors.forename: M
authors.initials: M
authors.lastname: Dugas
authors.forename: P M
authors.initials: PM
authors.lastname: Williams
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
authors.forename: U
authors.initials: U
authors.lastname: Bacher
authors.forename: H
authors.initials: H
authors.lastname: Löffler
authors.forename: C
authors.initials: C
authors.lastname: Haferlach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D020732:Cytogenetic Analysis; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C497422:KMT2A protein, human; D012333:RNA, Messenger; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase