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Distribution of 11q23 breakpoints within the MLL breakpoint cluster region
in de novo acute leukemia and in treatment-related acute myeloid leukemia:
correlation with scaffold attachment regions and topoisomerase II consensus
binding sites
PL Broeker, HG Super, MJ Thirman, H Pomykala, Y Yonebayashi, S Tanabe, N Zeleznik-Le and JD Rowley
Department of Medicine, University of Chicago, IL, USA.
A major unresolved question for 11q23 translocations involving MLL is the
chromosomal mechanism(s) leading to these translocations. We have mapped
breakpoints within the 8.3-kb BamHI breakpoint cluster region in 31
patients with acute lymphoblastic leukemia and acute myeloid leukemia (AML)
de novo and in 8 t-AML patients. In 23 of 31 leukemia de novo patients, MLL
breakpoints mapped to the centromeric half (4.57 kb) of the breakpoint
cluster region, whereas those in eight de novo patients mapped to the
telomeric half (3.87 kb). In contrast, only two t-AML breakpoints mapped in
the centromeric half, whereas six mapped in the telomeric half. The
difference in distribution of the leukemia de novo breakpoints is
statistically significant (P = .02). A similar difference in distribution
of breakpoints between de novo patients and t-AML patients has been
reported by others. We identified a low- or weak-affinity scaffold
attachment region (SAR) mapping just centromeric to the breakpoint cluster
region, and a high-affinity SAR mapping within the telomeric half of the
breakpoint cluster region. Using high stringency criteria to define in
vitro vertebrate topoisomerase II (topo II) consensus sites, one topo II
site mapped adjacent to the telomeric SAR, whereas six mapped within the
SAR. Therefore, 74% of leukemia de novo and 25% of t-AML breakpoints map to
the centromeric half of the breakpoint cluster region map between the two
SARs; in contrast, 26% of the leukemia de novo and 75% of the t-AML patient
breakpoints map to the telomeric half of the breakpoint cluster region that
contains both the telomeric SAR and the topo II sites. Thus, the chromatin
structure of the MLL breakpoint cluster region may be important in
determining the distribution of the breakpoints. The data suggest that the
mechanism(s) leading to translocations may differ in leukemia de novo and
in t-AML.
Volume 87,
Issue 5,
pp. 1912-1922,
03/01/1996
Copyright © 1996 by The American Society of Hematology
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105(5):
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|
|
|
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|
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|
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|
|
|
|
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|
|
|
|
|
|
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July 1, 1999;
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[Abstract]
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|
|
|
|
|
|
|
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6428 - 6433.
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[PDF]
|
|
|
|
|
|
|
P. L. Strissel, R. Strick, J. D. Rowley, and N. J. Zeleznik-Le
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November 15, 1998;
92(10):
3793 - 3803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Felix, A. H. Walker, B. J. Lange, T. M. Williams, N. J. Winick, N.-K. V. Cheung, B. D. Lovett, P. C. Nowell, I. A. Blair, and T. R. Rebbeck
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PNAS,
October 27, 1998;
95(22):
13176 - 13181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zucman-Rossi, P. Legoix, J.-M. Victor, B. Lopez, and G. Thomas
Chromosome translocation based on illegitimate recombination in human tumors
PNAS,
September 29, 1998;
95(20):
11786 - 11791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Gamou, E. Kitamura, F. Hosoda, K. Shimizu, K. Shinohara, Y. Hayashi, T. Nagase, Y. Yokoyama, and M. Ohki
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Blood,
June 1, 1998;
91(11):
4028 - 4037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Sugimoto, K. Yamada, M. Egashira, Y. Yazaki, H. Hirai, A. Kikuchi, and K. Oshimi
Temporal and Spatial Distribution of DNA Topoisomerase II Alters During Proliferation, Differentiation, and Apoptosis in HL-60 Cells
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February 15, 1998;
91(4):
1407 - 1417.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. B. Gale, A. M. Ford, R. Repp, A. Borkhardt, C. Keller, O. B. Eden, and M. F. Greaves
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PNAS,
December 9, 1997;
94(25):
13950 - 13954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. T. Look
Oncogenic Transcription Factors in the Human Acute Leukemias
Science,
November 7, 1997;
278(5340):
1059 - 1064.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. D. Megonigal, E. F. Rappaport, D. H. Jones, C. S. Kim, P. C. Nowell, B. J. Lange, and C. A. Felix
Panhandle PCR strategy to amplify MLL genomic breakpoints in treatment-related leukemias
PNAS,
October 14, 1997;
94(21):
11583 - 11588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Rowley, S. Reshmi, O. Sobulo, T. Musvee, J. Anastasi, S. Raimondi, N. R. Schneider, J. C. Barredo, E. S. Cantu, B. Schlegelberger, et al.
All Patients With the T(11; 16)(q23; p13.3) That Involves MLL and CBP Have Treatment-Related Hematologic Disorders
Blood,
July 15, 1997;
90(2):
535 - 541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Arai, F. Hosoda, H. Kobayashi, K. Arai, Y. Hayashi, N. Kamada, Y. Kaneko, and M. Ohki
The inv(11)(p15q22) Chromosome Translocation of De Novo and Therapy-Related Myeloid Malignancies Results in Fusion of the Nucleoporin Gene, NUP98, With the Putative RNA Helicase Gene, DDX10
Blood,
June 1, 1997;
89(11):
3936 - 3944.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. W. So, C. Caldas, M.-M. Liu, S.-J. Chen, Q.-H. Huang, L.-J. Gu, M. H. Sham, L. M. Wiedemann, and L. C. Chan
EEN encodes for a member of a new family of proteins containing an Src homology 3 domain and is the third gene located on chromosome 19p13 that fuses to MLL in human leukemia
PNAS,
March 18, 1997;
94(6):
2563 - 2568.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-P. Sim and L. F. Liu
Nucleolytic Cleavage of the Mixed Lineage Leukemia Breakpoint Cluster Region during Apoptosis
J. Biol. Chem.,
August 17, 2001;
276(34):
31590 - 31595.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Mao, S. D. Desai, C.-Y. Ting, J. Hwang, and L. F. Liu
26 S Proteasome-mediated Degradation of Topoisomerase II Cleavable Complexes
J. Biol. Chem.,
October 26, 2001;
276(44):
40652 - 40658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang, P. Strissel, R. Strick, J. Chen, G. Nucifora, M. M. Le Beau, R. A. Larson, and J. D. Rowley
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PNAS,
March 5, 2002;
99(5):
3070 - 3075.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Wiemels, R. N. Smith, G. M. Taylor, O. B. Eden, F. E. Alexander, M. F. Greaves, and United Kingdom Childhood Cancer Study Investigator
Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia
PNAS,
March 27, 2001;
98(7):
4004 - 4009.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Strick, P. L. Strissel, S. Borgers, S. L. Smith, and J. D. Rowley
From the Cover: Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia
PNAS,
April 25, 2000;
97(9):
4790 - 4795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
