Expression of Notch1 and mTOR pathway proteins in pediatric lymphoblastic lymphoma; a Children's Oncology Group report

Kristi J. Smock, Archana M. Agarwal, Megan S. Lim, Sheryl R. Tripp, Rodney R. Miles, Jay L. Patel, Minnie Abromowitch, Mark A. Lones, Mitchell S. Cairo, Sherrie L. Perkins

Research output: Contribution to journalArticle

Abstract

Acute lymphoblastic leukemia (ALL) and lymphoma (LBL) represent a disease spectrum. Activating mutations in Notch1 are found in 50-60 % of T-cell ALL, and little is known about its role in B-cell ALL. Notch1 activation results in upregulation of the mammalian target of rapamycin (mTOR) pathway. Expression of mTOR and downstream targets has not been characterized in LBL. We analyzed immunohistochemical expression of Notch1, phospho-mTOR, phospho-70S6 kinase, and phospho-S6 ribosomal protein in 15 cases of T-cell LBL and 10 cases of B-cell LBL obtained from Children's Oncology Group trial CCG 5971. Positive specimens were defined as ≥25 % expression. All specimens expressed Notch1 and most expressed phospho-mTOR and phospho-70S6 kinase, while a minority expressed phospho-S6 ribosomal protein. Our data suggest that expression of both the Notch1 and mTOR pathways are increased in T-cell and B-cell pediatric LBL and support further studies in determining the therapeutic role of Notch1 and mTOR inhibitors.

Original languageEnglish (US)
Pages (from-to)9-14
Number of pages6
JournalJournal of Hematopathology
Volume7
Issue number1
DOIs
StatePublished - Mar 2014

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TOR Serine-Threonine Kinases
Sirolimus
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
B-Lymphocytes
Ribosomal Protein S6
Ribosomal Protein S6 Kinases
T-Lymphocytes
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Phosphotransferases
Up-Regulation
Mutation

Keywords

  • Acute lymphoblastic leukemia (ALL)
  • Immunohistochemistry
  • Lymphoblastic lymphoma (LBL)
  • Mammalian target of rapamycin (mTOR)
  • Notch1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Hematology

Cite this

Smock, K. J., Agarwal, A. M., Lim, M. S., Tripp, S. R., Miles, R. R., Patel, J. L., ... Perkins, S. L. (2014). Expression of Notch1 and mTOR pathway proteins in pediatric lymphoblastic lymphoma; a Children's Oncology Group report. Journal of Hematopathology, 7(1), 9-14. https://doi.org/10.1007/s12308-014-0200-9

Expression of Notch1 and mTOR pathway proteins in pediatric lymphoblastic lymphoma; a Children's Oncology Group report. / Smock, Kristi J.; Agarwal, Archana M.; Lim, Megan S.; Tripp, Sheryl R.; Miles, Rodney R.; Patel, Jay L.; Abromowitch, Minnie; Lones, Mark A.; Cairo, Mitchell S.; Perkins, Sherrie L.

In: Journal of Hematopathology, Vol. 7, No. 1, 03.2014, p. 9-14.

Research output: Contribution to journalArticle

Smock, KJ, Agarwal, AM, Lim, MS, Tripp, SR, Miles, RR, Patel, JL, Abromowitch, M, Lones, MA, Cairo, MS & Perkins, SL 2014, 'Expression of Notch1 and mTOR pathway proteins in pediatric lymphoblastic lymphoma; a Children's Oncology Group report', Journal of Hematopathology, vol. 7, no. 1, pp. 9-14. https://doi.org/10.1007/s12308-014-0200-9
Smock, Kristi J. ; Agarwal, Archana M. ; Lim, Megan S. ; Tripp, Sheryl R. ; Miles, Rodney R. ; Patel, Jay L. ; Abromowitch, Minnie ; Lones, Mark A. ; Cairo, Mitchell S. ; Perkins, Sherrie L. / Expression of Notch1 and mTOR pathway proteins in pediatric lymphoblastic lymphoma; a Children's Oncology Group report. In: Journal of Hematopathology. 2014 ; Vol. 7, No. 1. pp. 9-14.
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