PMID- 9763573
OWN - NLM
STAT- MEDLINE
DCOM- 19981109
LR  - 20210924
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 92
IP  - 8
DP  - 1998 Oct 15
TI  - CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: 
      association with prior therapy.
PG  - 2879-85
AB  - CBFA2(AML1) has emerged as a gene critical in hematopoiesis; its protein product 
      forms the DNA-binding subunit of the heterodimeric core-binding factor (CBF) that 
      binds to the transcriptional regulatory regions of genes, some of which are 
      active specifically in hematopoiesis. CBFA2 forms a fusion gene with ETO and 
      MDS1/EVI1 in translocations in myeloid leukemia and with ETV6(TEL) in the 
      t(12;21) common in childhood pre-B acute lymphoblastic leukemia. We have analyzed 
      samples from 30 leukemia patients who had chromosome rearrangements involving 
      21q22 by using fluorescence in situ hybridization (FISH). Our analysis showed 
      that 7 of them involved CBFA2 and new translocation partners. Two patients had a 
      t(17;21)(q11.2;q22), whereas the other 5 had translocations involving 1p36, 5q13, 
      12q24, 14q22, or 15q22. Five of these novel breakpoints in CBFA2 occurred in 
      intron 6; this same intron is involved in the t(3;21). One breakpoint mapped to 
      the t(8;21) breakpoint region in intron 5, and 1 mapped 5' to that region. All 7 
      CBFA2 rearrangements resulted from balanced translocations. All 7 patients had 
      myeloid disorders (acute myeloid leukemia or myelodysplastic syndrome); 2 were de 
      novo and 5 had treatment histories that included topoisomerase II targeting 
      agents. The association of therapy-related disorders with translocations 
      involving CBFA2 was significant by Fisher's exact test (P < .003). These results 
      provide further evidence that this region of CBFA2 is susceptible to breakage in 
      cells exposed to topoisomerase II inhibitors.
CI  - Copyright 1998 by The American Society of Hematology.
FAU - Roulston, D
AU  - Roulston D
AD  - Section of Hematology/Oncology, Department of Medicine, and the Cancer Research 
      Center, The University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
FAU - Espinosa, R 3rd
AU  - Espinosa R 3rd
FAU - Nucifora, G
AU  - Nucifora G
FAU - Larson, R A
AU  - Larson RA
FAU - Le Beau, M M
AU  - Le Beau MM
FAU - Rowley, J D
AU  - Rowley JD
LA  - eng
GR  - CA40046/CA/NCI NIH HHS/United States
GR  - CA42557/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Chromosomes, Human/genetics/*ultrastructure
MH  - Chromosomes, Human, Pair 1/genetics/ultrastructure
MH  - Chromosomes, Human, Pair 12/genetics/ultrastructure
MH  - Chromosomes, Human, Pair 14/genetics/ultrastructure
MH  - Chromosomes, Human, Pair 15/genetics/ultrastructure
MH  - Chromosomes, Human, Pair 17/genetics/ultrastructure
MH  - Chromosomes, Human, Pair 21/genetics/*ultrastructure
MH  - Chromosomes, Human, Pair 5/genetics/ultrastructure
MH  - Core Binding Factor Alpha 2 Subunit
MH  - *DNA-Binding Proteins
MH  - Humans
MH  - Leukemia, Myeloid/drug therapy/*genetics/pathology
MH  - Myelodysplastic Syndromes/genetics/pathology
MH  - *Proto-Oncogene Proteins
MH  - Transcription Factors/*genetics
MH  - *Translocation, Genetic
EDAT- 1998/10/09 02:00
MHDA- 2001/03/28 10:01
CRDT- 1998/10/09 02:00
PHST- 1998/10/09 02:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/10/09 02:00 [entrez]
AID - S0006-4971(20)76208-7 [pii]
PST - ppublish
SO  - Blood. 1998 Oct 15;92(8):2879-85.