Ectopic expression of the proto-oncogene Mer in pediatric T-cell acute lymphoblastic leukemia.
OBJECTIVE
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.


METHODS
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.
Graham
Douglas K
DK
Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA. doug.graham@uchsc.edu
Salzberg
Dana B
DB
Kurtzberg
Joanne
J
Sather
Susan
S
Matsushima
Glenn K
GK
Keating
Amy K
AK
Liang
Xiayuan
X
Lovell
Mark A
MA
Williams
Sara A
SA
Dawson
Thomas L
TL
Schell
Michael J
MJ
Anwar
Adil A
AA
Snodgrass
H Ralph
HR
Earp
H Shelton
HS