|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1728-1734
Partial Tandem Duplications of the MLL Gene Are Detectable in
Peripheral Blood and Bone Marrow of Nearly All Healthy Donors
Susanne Schnittger,
Bernhard Wörmann,
Wolfgang Hiddemann, and
Frank Griesinger
From the Department of Hematology and Oncology, University of
Göttingen, Göttingen, Germany.
Partial tandem duplication within the MLL gene has recently been
described as a novel genetic alteration in acute myeloid leukemia
(AML). It has been associated with trisomy of chromosome 11, but was
also identified in AML patients with normal karyotypes. The current
study was performed to investigate whether MLL duplications are
restricted to AML, and hence whether they may also occur in normal
hematopoietic cells. MLL-duplication transcripts were analyzed by
nested reverse-transcriptase polymerase chain reaction (RT-PCR) in
peripheral blood in two groups of 45 and 20 patients, respectively, as
well as in two bone marrow samples from healthy volunteers. Duplications were detected in two independent nested RT-PCR experiments in the peripheral blood samples of 38 of 45 (84%) and 20 of 20 (100%)
of the two groups and in both bone marrow samples. On this basis, MLL
duplications seem to occur frequently in a subset of cells in normal
hematopoiesis. The type of partially duplicated MLL transcripts varied
substantially. Three transcripts were identical to those known from
AML. In addition, four new transcripts were characterized. Three of
these four were in frame and potentially translatable. MLL duplications
were also detected by seminested genomic PCR with intron 9- and intron
1-specific primers in 20 of 20 peripheral blood samples studied,
indicating that the duplications are genomically fixed at the DNA level
and are not an RT-PCR artifact. In summary, MLL duplications are
regularly generated by homologous ALU recombination in a small number
of hematopoietic cells of most or even all healthy donors. These data
suggest that MLL duplications are not implicated in the malignant
transformation in AML, or alternatively, that only a few cells will
acquire additional oncogenic mutations necessary to establish the
malignant phenotype of AML.
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. Ozeki, H. Kiyoi, Y. Hirose, M. Iwai, M. Ninomiya, Y. Kodera, S. Miyawaki, K. Kuriyama, C. Shimazaki, H. Akiyama, et al.
Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia
Blood,
March 1, 2004;
103(5):
1901 - 1908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Libura, V. Asnafi, A. Tu, E. Delabesse, I. Tigaud, F. Cymbalista, A. Bennaceur-Griscelli, P. Villarese, G. Solbu, A. Hagemeijer, et al.
FLT3 and MLL intragenic abnormalities in AML reflect a common category of genotoxic stress
Blood,
September 15, 2003;
102(6):
2198 - 2204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P F Ravetto, R Agarwal, M L Chiswick, S W D'Souza, O B Eden, and G M Taylor
Absence of leukaemic fusion gene transcripts in preterm infants exposed to diagnostic x rays
Arch. Dis. Child. Fetal Neonatal Ed.,
May 1, 2003;
88(3):
F237 - F244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Dohner, K. Tobis, R. Ulrich, S. Frohling, A. Benner, R. F. Schlenk, and H. Dohner
Prognostic Significance of Partial Tandem Duplications of the MLL Gene in Adult Patients 16 to 60 Years Old With Acute Myeloid Leukemia and Normal Cytogenetics: A Study of the Acute Myeloid Leukemia Study Group Ulm
J. Clin. Oncol.,
August 1, 2002;
20(15):
3254 - 3261.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Kuwada, F. Kimura, T. Matsumura, T. Yamashita, Y. Nakamura, N. Wakimoto, T. Ikeda, K. Sato, and K. Motoyoshi
t(11;14)(q23;q24) Generates an MLL-Human Gephyrin Fusion Gene along with a de facto Truncated MLL in Acute Monoblastic Leukemia
Cancer Res.,
March 1, 2001;
61(6):
2665 - 2669.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Eguchi-Ishimae, M. Eguchi, E. Ishii, S. Miyazaki, K. Ueda, N. Kamada, and S. Mizutani
Breakage and fusion of the TEL (ETV6) gene in immature B lymphocytes induced by apoptogenic signals
Blood,
February 1, 2001;
97(3):
737 - 743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. P. Whitman, M. P. Strout, G. Marcucci, A. G. Freud, L. L. Culley, N. J. Zeleznik-Le, K. Mrózek, K. S. Theil, U. R. Kees, C. D. Bloomfield, et al.
The Partial Nontandem Duplication of the MLL (ALL1) Gene Is a Novel Rearrangement That Generates Three Distinct Fusion Transcripts in B-Cell Acute Lymphoblastic Leukemia
Cancer Res.,
January 1, 2001;
61(1):
59 - 63.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. A. Felix and B. J. Lange
Leukemia in Infants
Oncologist,
June 1, 1999;
4(3):
225 - 240.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M.-H. Kim-Rouille, A. MacGregor, L.M. Wiedemann, M.F. Greaves, C. Navarrete;, and F. M. Uckun
MLL-AF4 Gene Fusions in Normal Newborns
Blood,
February 1, 1999;
93(3):
1107 - 1110.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Megonigal, N.-K. V. Cheung, E. F. Rappaport, P. C. Nowell, R. B. Wilson, D. H. Jones, K. Addya, D. G. B. Leonard, B. H. Kushner, T. M. Williams, et al.
Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors
PNAS,
March 14, 2000;
97(6):
2814 - 2819.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
