PMID- 7533526
OWN - NLM
STAT- MEDLINE
DCOM- 19950413
LR  - 20191023
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 11
IP  - 4
DP  - 1994 Dec
TI  - AML1 fusion transcripts in t(3;21) positive leukemia: evidence of molecular 
      heterogeneity and usage of splicing sites frequently involved in the generation 
      of normal AML1 transcripts.
PG  - 226-36
AB  - The t(3;21)(q26;q22) is associated with chronic myelogenous leukemia in blast 
      crisis (CML-BC), leukemia evolving from (therapy-related) myelodysplasia, and 
      with leukemia following other hematopoietic proliferative diseases. Molecular 
      cytogenetic analysis and cloning of a few t(3;21) cases indicate that the 
      breakpoints are quite heterogeneous even within a specific clinical phenotype. 
      Interestingly some of the (3;21) breakpoints involve the AML1 gene previously 
      found rearranged in the t(8;21) associated with acute myelogenous leukemia. AML1 
      is related to the Drosophila gene runt and is the human counterpart of the gene 
      for the alpha subunit of the nuclear polyoma enhancer binding protein (PEBP2) 
      also known as the core binding factor (CBF). In the t(3;21) AML1 was found 
      rearranged with EAP, a gene on chromosome 3 encoding a small ribosomal protein, 
      as well as with EV11, another gene on chromosome 3. Here we report our study of 
      six cases of t(3;21). By using fluorescence in situ hybridization (FISH) analysis 
      and AML1 probes we could conclude that at least in two CML-BC cases the 
      breakpoint occurred in the AML1 intron that is disrupted by the t(8;21). An 
      AML1/EAP fusion transcript, different from the one described in a therapy-related 
      myelodysplasia, was detected in both CML-BC cases. This transcript is expected to 
      result in a predicted protein containing the AML1 nuclear binding domain with an 
      attached stretch of 17 amino acids unrelated to the EAP small ribosomal protein. 
      In the other t(3;21) patients we could not detect an AML1/EAP transcript or an 
      AML1/EV11 transcript. This result suggests heterogeneity of the t(3;21) at the 
      molecular level. The AML1 chimeric transcripts identified so far, both in the 
      t(3;21) and in the t(8;21), diverge from the normal transcripts either after exon 
      5 or exon 6. Here we show that in normal AML1 transcripts different splicing 
      events are seen to occur after AML1 exon 5 as well as exon 6.
FAU - Sacchi, N
AU  - Sacchi N
AD  - Department of Biology and Genetics, School of Medicine, University of Milan, 
      Italy.
FAU - Nisson, P E
AU  - Nisson PE
FAU - Watkins, P C
AU  - Watkins PC
FAU - Faustinella, F
AU  - Faustinella F
FAU - Wijsman, J
AU  - Wijsman J
FAU - Hagemeijer, A
AU  - Hagemeijer A
LA  - eng
SI  - GENBANK/S76343
SI  - GENBANK/S76345
SI  - GENBANK/S76346
SI  - GENBANK/S76350
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (DNA Probes)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
GS  - AML1
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Blast Crisis/*genetics/pathology
MH  - Chromosome Banding
MH  - Chromosomes, Human, Pair 21
MH  - Chromosomes, Human, Pair 3
MH  - Cloning, Molecular
MH  - Core Binding Factor Alpha 2 Subunit
MH  - DNA Probes
MH  - *DNA-Binding Proteins
MH  - Exons
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/pathology
MH  - Leukemia, Myeloid, Acute/*genetics/pathology
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/chemistry/*genetics
MH  - *Proto-Oncogene Proteins
MH  - *RNA Splicing
MH  - RNA, Messenger/genetics
MH  - Recombinant Fusion Proteins/chemistry/genetics
MH  - *Transcription Factors
MH  - *Translocation, Genetic
EDAT- 1994/12/01 00:00
MHDA- 1994/12/01 00:01
CRDT- 1994/12/01 00:00
PHST- 1994/12/01 00:00 [pubmed]
PHST- 1994/12/01 00:01 [medline]
PHST- 1994/12/01 00:00 [entrez]
AID - 10.1002/gcc.2870110405 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 1994 Dec;11(4):226-36. doi: 10.1002/gcc.2870110405.