PMID- 16675557
OWN - NLM
STAT- MEDLINE
DCOM- 20060821
LR  - 20220311
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 12
IP  - 9
DP  - 2006 May 1
TI  - Ectopic expression of the proto-oncogene Mer in pediatric T-cell acute 
      lymphoblastic leukemia.
PG  - 2662-9
AB  - PURPOSE: The Mer receptor tyrosine kinase, cloned from a B-lymphoblastoid 
      library, is the mammalian orthologue of the chicken retroviral oncogene v-eyk and 
      sends antiapoptotic and transforming signals when activated. To determine if Mer 
      expression is ectopic in T-cell acute lymphoblastic leukemia (ALL) and 
      potentially important in leukemogenesis, we analyzed Mer expression in normal 
      human thymocytes and lymphocytes and in pediatric ALL patient samples. 
      EXPERIMENTAL DESIGN: Reverse transcription-PCR, flow cytometry, and 
      immunohistochemistry were used to determine expression of Mer in sorted human 
      thymocyte populations, lymphocytes, and lymphocytes activated by 
      phytohemagglutinin or phorbol 12-myristate 13-acetate/ionophore. Mer expression 
      in 34 T-cell ALL (T-ALL) patient samples was evaluated by reverse 
      transcription-PCR, and Mer protein expression in a separate cohort of 16 patient 
      samples was assayed by flow cytometry and Western blot. RESULTS: Mer expression 
      was absent in normal thymocytes or lymphocytes, and in T cells activated with 
      phytohemagglutinin or phorbol 12-myristate 13-acetate/ionophore. In contrast, 
      Jurkat cells and T-ALL patient samples expressed unique 180 to 185 kDa Mer 
      protein glycoforms. Substantial Mer RNA levels were principally observed in a 
      subset of T-ALL patient samples that expressed B220 (P = 0.004) but lacked 
      surface expression of CD3 (P = 0.02) and CD4 (P = 0.006), a phenotypic profile 
      consistent with immature lymphoblasts. In addition, 8 of 16 T-ALL patient samples 
      had Mer protein detected by flow cytometry and Western blot. CONCLUSIONS: 
      Transforming Mer signals may contribute to T-cell leukemogenesis, and abnormal 
      Mer expression may be a novel therapeutic target in pediatric ALL therapy.
FAU - Graham, Douglas K
AU  - Graham DK
AD  - Department of Pediatrics, University of Colorado Health Sciences Center, Denver, 
      Colorado, USA. doug.graham@uchsc.edu
FAU - Salzberg, Dana B
AU  - Salzberg DB
FAU - Kurtzberg, Joanne
AU  - Kurtzberg J
FAU - Sather, Susan
AU  - Sather S
FAU - Matsushima, Glenn K
AU  - Matsushima GK
FAU - Keating, Amy K
AU  - Keating AK
FAU - Liang, Xiayuan
AU  - Liang X
FAU - Lovell, Mark A
AU  - Lovell MA
FAU - Williams, Sara A
AU  - Williams SA
FAU - Dawson, Thomas L
AU  - Dawson TL
FAU - Schell, Michael J
AU  - Schell MJ
FAU - Anwar, Adil A
AU  - Anwar AA
FAU - Snodgrass, H Ralph
AU  - Snodgrass HR
FAU - Earp, H Shelton
AU  - Earp HS
LA  - eng
GR  - T32 CA082086/CA/NCI NIH HHS/United States
GR  - P30 CA46934/CA/NCI NIH HHS/United States
GR  - T32CA8608604/CA/NCI NIH HHS/United States
GR  - CA 68346/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Neoplasm)
RN  - EC 2.7.10.1 (MERTK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (c-Mer Tyrosine Kinase)
SB  - IM
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Infant
MH  - Jurkat Cells
MH  - Leukemia-Lymphoma, Adult T-Cell/*genetics/pathology
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/*genetics
MH  - RNA, Neoplasm/genetics
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/immunology/pathology
MH  - Transcription, Genetic
MH  - c-Mer Tyrosine Kinase
EDAT- 2006/05/06 09:00
MHDA- 2006/08/22 09:00
CRDT- 2006/05/06 09:00
PHST- 2006/05/06 09:00 [pubmed]
PHST- 2006/08/22 09:00 [medline]
PHST- 2006/05/06 09:00 [entrez]
AID - 12/9/2662 [pii]
AID - 10.1158/1078-0432.CCR-05-2208 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2006 May 1;12(9):2662-9. doi: 10.1158/1078-0432.CCR-05-2208.