Lifelong persistence of AML associated MLL partial tandem duplications (MLL-PTD) in healthy adults.
AML-associated MLL-PTD contribute to leukemogenesis by a gain of function and confer an unfavorable prognosis. Like other leukemia associated aberrations they are also present in healthy adults. To delineate the leukemogenic mechanism we tracked down MLL-PTD in normal hematopoiesis and investigated cord blood samples. MLL-PTD were observed in 56/60 (93%) of all cord bloods. In contrast to AML, the transcript frequency in cord blood was four log scales lower as determined by real-time PCR. The CD34+ progenitor cell, CD33+ myeloid, CD19+ B-lymphoid and CD3+ T-lymphoid subfractions were positive. The ubiquitous presence of MLL-PTD in cord blood implicates a lifelong exposure, not an accumulation during lifetime. Since also present in the stem cell subfraction, these factors seem not to be major determinants in MLL-PTD leukemogenesis.
Bäsecke
Jörg
J
Department of Hematology and Oncology, University of Goettingen, Goettingen, Germany. jbaesec@gwdg.de
Podleschny
Martina
M
Clemens
Robert
R
Schnittger
Susanne
S
Viereck
Volker
V
Trümper
Lorenz
L
Griesinger
Frank
F
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D020440:Gene Duplication; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase