Dlk1 in normal and abnormal hematopoiesis.
Dlk1 (Pref-1) is a transmembrane and secreted protein, which is a member of the epidermal growth factor-like family, homologous to Notch/Delta/Serrate. We have found by real-time RT-PCR that Dlk1 mRNA levels were high in CD34(+) cells in 10 of 12 MDS samples compared with CD34(+) cells from 11 normals. Also, Dlk1 mRNA was elevated in mononuclear, low density bone marrow cells from 11/38 MDS patients, 5/11 AML M6 and 2/4 AML M7 samples. Furthermore, 5/6 erythroleukemia and 2/2 megakaryocytic leukemia cell lines highly expressed Dlk1 mRNA. Levels of Dlk1 mRNA markedly increased during megakaryocytic differentiation of both CMK megakaryoblasts as well as normal CD34(+) hematopoietic stem cells. High serum levels of Dlk1 occurred in RA (4/10) and essential thrombocythemia (2/10) patients. Functional studies showed that forced expression of Dlk1 enhanced proliferation of K562 cells growing in 1% fetal bovine serum. Analysis of hematopoiesis of Dlk1 knockout mice suggested that Dlk1 contributed to granulocyte, megakaryocyte and B-cell clonogenic growth and was needed for generation of splenic B-cells. In summary, Dlk1 is overexpressed in selected samples of MDS (especially RA and RAEB) and AML (particularly M6, M7), and it appears to be associated with normal development of megakaryocytes and B cells.
Sakajiri
S
S
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA, Los Angeles, CA 90048, USA.
O'kelly
J
J
Yin
D
D
Miller
C W
CW
Hofmann
W K
WK
Oshimi
K
K
Shih
L-Y
LY
Kim
K-H
KH
Sul
H S
HS
Jensen
C H
CH
Teisner
B
B
Kawamata
N
N
Koeffler
H P
HP
D000818:Animals; D018952:Antigens, CD34; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002999:Clone Cells / Q000473:pathology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000097:blood / Q000235:genetics* / Q000502:physiology; D006402:Hematologic Diseases / Q000473:pathology*; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000473:pathology; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018952:Antigens, CD34; D006023:Glycoproteins; D012333:RNA, Messenger