title: Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization.
abstract: Acute leukemias of ambiguous lineage represent a heterogeneous group of rare, poorly characterized leukemias with adverse outcome. No larger studies have yet performed a combined approach of molecular and clinical characterization of acute undifferentiated leukemia (AUL) and biphenotypic acute leukemia (BAL) in adults. Here we describe 16 adults with AUL and 26 with BAL and performed mutational as well as expression studies of genes with prognostic impact in acute leukemia (BAALC, ERG, MN1, WT1, and IGFBP7). AUL showed overexpression of these genes compared to T-lymphoblastic leukemia (T-ALL), B-precursor ALL, and to acute myeloid leukemia (AML). Genotype alterations were not detectable in AUL. BAL samples were characterized by frequent WT1 mutations (18 %) and BCR-ABL translocations (30 %). ALL-based treatment protocols induced complete remissions in 40 % and AML-like therapies in 22 % of AUL/BAL patients. The outcome in both groups was very poor; a long-term survival was only observed in patients undergoing allogeneic stem cell transplantation (SCT). Our findings indicate that AUL and BAL share important molecular and high-risk features of both myeloid and lymphoid leukemias. BAL patients exhibited genetic alterations, which can be targeted therapeutically. Importantly, ALL therapy might be more effective than AML protocols and AUL/BAL patients should be considered for allogeneic SCT.
authors: Department of Hematology, Oncology and Tumor Immunology, Charité University Hospital Berlin, Hindenburgdamm 30, 12203, Campus Benjamin Franklin, Berlin, Germany.
authors: Sandra
authors: S
authors: Heesch
authors: Martin
authors: M
authors: Neumann
authors: Stefan
authors: S
authors: Schwartz
authors: Isabelle
authors: I
authors: Bartram
authors: Cornelia
authors: C
authors: Schlee
authors: Thomas
authors: T
authors: Burmeister
authors: Matthias
authors: M
authors: Hänel
authors: Arnold
authors: A
authors: Ganser
authors: Michael
authors: M
authors: Heuser
authors: Clemens-Martin
authors: CM
authors: Wendtner
authors: Wolfgang E
authors: WE
authors: Berdel
authors: Nicola
authors: N
authors: Gökbuget
authors: Dieter
authors: D
authors: Hoelzer
authors: Wolf-Karsten
authors: WK
authors: Hofmann
authors: Eckhard
authors: E
authors: Thiel
authors: Claudia D
authors: CD
authors: Baldus
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019070:Cell Lineage; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D007938:Leukemia / Q000145:classification / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D015456:Leukemia, Biphenotypic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D022423:Myeloid Cells / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D011379:Prognosis; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins