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Published in: Cancer Immunology, Immunotherapy 1/2010

01-01-2010 | Original Article

Expression of CD13/aminopeptidase N in precursor B-cell leukemia: role in growth regulation of B cells

Authors: Ankit Saxena, Ambak Rai, Vinod Raina, Tulika Seth, Dipendra Kumar Mitra

Published in: Cancer Immunology, Immunotherapy | Issue 1/2010

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Abstract

Expression of cell surface CD13 in acute B-cell leukemia (ALL-B) is often viewed, as an aberrant expression of a myeloid lineage marker. Here, we attempted to study the stage specific expression of CD13 on ALL-B blasts and understand its role in leukemogenesis as pertaining to stage of B-cell ontogeny. A total of 355 cases of different hematological malignancies were diagnosed by immunophenotyping. Among 68 cases of early B-cell ALL, 22 cases with distinct immunophenotype was identified as immature B-cell ALL. Blasts from these ALL-B patients demonstrated prominent expression of CD10, CD19, CD22, but neither cytoplasmic nor surface IgM receptors. This strongly indicates leukemogenesis at an early stage of B-cell development. We also identified, the existence of a subpopulation of cells with remarkably similar phenotype in non-leukemic marrow from healthy subjects (expressing CD10, CD19, CD22, CD24, Tdt together with the co-expression of CD13). This sub-population of B cells concomitantly expressing CD13 appeared to be a highly proliferating group. By blocking their cell surface CD13 in leukemic blasts with monoclonal antibody we were able to inhibit their proliferation. We hypothesized that neoplastic transformation at this stage may be facilitated by CD13. CD13 may thus be an important target for novel molecular therapy of early stage acute B-cell leukemia.
Literature
1.
go back to reference Amoscato AA, Alexander JW, Babcock GF (1989) Surface aminopeptidase activity of human lymphocytes. J Immunol 142:1245–1252PubMed Amoscato AA, Alexander JW, Babcock GF (1989) Surface aminopeptidase activity of human lymphocytes. J Immunol 142:1245–1252PubMed
2.
go back to reference Antczak C, De Meester I, Bauvois B (2001) Ectopeptidases in pathophysiology. Bioessays 23:251–260CrossRefPubMed Antczak C, De Meester I, Bauvois B (2001) Ectopeptidases in pathophysiology. Bioessays 23:251–260CrossRefPubMed
3.
go back to reference Bank U, Kruger S, Langner J, Roessner A (2000) Review: peptidases and peptidase inhibitors in the pathogenesis of diseases. Disturbances in the ubiquitin-mediated proteolytic system. Protease-antiprotease imbalance in inflammatory reactions. Role of cathepsins in tumour progression. Adv Exp Med Biol 477:349–378CrossRefPubMed Bank U, Kruger S, Langner J, Roessner A (2000) Review: peptidases and peptidase inhibitors in the pathogenesis of diseases. Disturbances in the ubiquitin-mediated proteolytic system. Protease-antiprotease imbalance in inflammatory reactions. Role of cathepsins in tumour progression. Adv Exp Med Biol 477:349–378CrossRefPubMed
4.
go back to reference Ciudad J, Orfao A, Vidriales B et al (1998) Immunophenotypic analysis of CD19+ precursors in normal human adult bone marrow: implications for minimal residual disease detection. Hematologica 83:1069–1075 Ciudad J, Orfao A, Vidriales B et al (1998) Immunophenotypic analysis of CD19+ precursors in normal human adult bone marrow: implications for minimal residual disease detection. Hematologica 83:1069–1075
5.
go back to reference Goodnow CC, Cyster JG, Hartleyk SB, Bell SE et al (1995) Self tolerant checkpoints in B lymphocyte development. Adv immunol 59:279 Goodnow CC, Cyster JG, Hartleyk SB, Bell SE et al (1995) Self tolerant checkpoints in B lymphocyte development. Adv immunol 59:279
6.
go back to reference Mirro J, Zipf TF, Pui CH, Kitchingman G, Williams D, Melvin S, Murphy SB, Stass S (1985) Acute mixed lineage leukemia: clinicopathologic correlations and prognostic significance. Blood 66:1115–1123 Mirro J, Zipf TF, Pui CH, Kitchingman G, Williams D, Melvin S, Murphy SB, Stass S (1985) Acute mixed lineage leukemia: clinicopathologic correlations and prognostic significance. Blood 66:1115–1123
7.
go back to reference Kramer MD, Simon MM (1987) Are proteinases functional molecules of T lymphocytes? Immunol Today 8:140CrossRef Kramer MD, Simon MM (1987) Are proteinases functional molecules of T lymphocytes? Immunol Today 8:140CrossRef
8.
9.
go back to reference Look AT, Ashmun RA, Shapiro LH, Peiper SC (1989) Human myeloid plasma membrane glycoprotein CD13 (gpl50) is identical to aminopeptidase N. J Clin Invest 83:1299 Look AT, Ashmun RA, Shapiro LH, Peiper SC (1989) Human myeloid plasma membrane glycoprotein CD13 (gpl50) is identical to aminopeptidase N. J Clin Invest 83:1299
10.
go back to reference McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH (2001) Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood 98(8):2498–2507 McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH (2001) Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood 98(8):2498–2507
11.
go back to reference Mishima Y, Mishima YM, Terui Y, Katsuyama M, Yamada M, Mori M et al (2002) Leukemic cell-surface CD13/aminopeptidase N and resistance to apoptosis mediated by endothelial cells. J Natl Cancer Inst 94:13 Mishima Y, Mishima YM, Terui Y, Katsuyama M, Yamada M, Mori M et al (2002) Leukemic cell-surface CD13/aminopeptidase N and resistance to apoptosis mediated by endothelial cells. J Natl Cancer Inst 94:13
12.
go back to reference Moody TW, Chan D, Fahrenkrug J, Jensen RT (2003) Neuropeptides as autocrine growth factors in cancer cells. Curr Pharm Des 9:495–509CrossRefPubMed Moody TW, Chan D, Fahrenkrug J, Jensen RT (2003) Neuropeptides as autocrine growth factors in cancer cells. Curr Pharm Des 9:495–509CrossRefPubMed
13.
go back to reference Nanus DM (2003) Of peptides and peptidases: the role of cell surface peptidases in cancer. Clin Cancer Res 9:6307–6309PubMed Nanus DM (2003) Of peptides and peptidases: the role of cell surface peptidases in cancer. Clin Cancer Res 9:6307–6309PubMed
14.
go back to reference Nanus DM, Shen R, Dai J, Sumitomo M (2001) Neutral endopeptidase and other peptidases such as aminopeptidase A and dipeptidyl peptidase IV in the development and progression of cancer. In: Mizutani S, Turner AJ, Nomura S, Ino K (eds) Cell-surface aminopeptidases: basic and clinical aspects. Elsevier, Amsterdam, pp 119–128 Nanus DM, Shen R, Dai J, Sumitomo M (2001) Neutral endopeptidase and other peptidases such as aminopeptidase A and dipeptidyl peptidase IV in the development and progression of cancer. In: Mizutani S, Turner AJ, Nomura S, Ino K (eds) Cell-surface aminopeptidases: basic and clinical aspects. Elsevier, Amsterdam, pp 119–128
15.
go back to reference Rolink AG, Andersson J, Melchers F (2004) Molecular mechanism guiding late stages of B-cell development. Immunol Rev 197(1):41–50CrossRefPubMed Rolink AG, Andersson J, Melchers F (2004) Molecular mechanism guiding late stages of B-cell development. Immunol Rev 197(1):41–50CrossRefPubMed
16.
go back to reference Riemann D, Kehlen A, Langner J (1999) CD13—not just a marker in leukemia typing. Immunol Today 20(2):83–88CrossRefPubMed Riemann D, Kehlen A, Langner J (1999) CD13—not just a marker in leukemia typing. Immunol Today 20(2):83–88CrossRefPubMed
17.
go back to reference Shipp MA, Look T (1993) Hematopoetic differentiation antigens that are membrane-associated enzymes: cutting is the key. Blood 82:1052–1070PubMed Shipp MA, Look T (1993) Hematopoetic differentiation antigens that are membrane-associated enzymes: cutting is the key. Blood 82:1052–1070PubMed
18.
go back to reference Borowitz MJ, Guenther KL, Shults KE, Stelzer GT (1993) Immuno-phenotyping of acute leukemia by flow cytometric analysis. Use of CD45 and right-angle light scatter to gate on leukemic blasts in three-color analysis. Am J Clin Pathol 100:534PubMed Borowitz MJ, Guenther KL, Shults KE, Stelzer GT (1993) Immuno-phenotyping of acute leukemia by flow cytometric analysis. Use of CD45 and right-angle light scatter to gate on leukemic blasts in three-color analysis. Am J Clin Pathol 100:534PubMed
19.
go back to reference Sobol RE, Royston I, LeBien TW et al (1985) Adult acute lymphoblastic leukemia phenotypes defined by monoclonal antibodies. Blood 65(3):730–735PubMed Sobol RE, Royston I, LeBien TW et al (1985) Adult acute lymphoblastic leukemia phenotypes defined by monoclonal antibodies. Blood 65(3):730–735PubMed
20.
go back to reference Shipp MA, Vijayaraghaven J, Schmidt EV, Masteller EL, Dadamio L, Hersh LB, Reinherz EL (1989) Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.1 1 (“enkephalinase”): direct evidence by cDNA transfection analysis. Proc Natl Acad Sci USA 86:297CrossRefPubMed Shipp MA, Vijayaraghaven J, Schmidt EV, Masteller EL, Dadamio L, Hersh LB, Reinherz EL (1989) Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.1 1 (“enkephalinase”): direct evidence by cDNA transfection analysis. Proc Natl Acad Sci USA 86:297CrossRefPubMed
21.
go back to reference Schon E, Jahn S, Kiessig ST, Demuth H-U, Neubert E, Barth A, Baehr RV, Ansorage S (1987) The role of dipeptidyl peptidase IV in human T lymphocyte activation. Inhibitors and antibodies against dipeptidyl peptidase IV suppresses lymphocyte proliferation and immunoglobulin synthesis in vitro. Eur J Immunol 17:18–21CrossRef Schon E, Jahn S, Kiessig ST, Demuth H-U, Neubert E, Barth A, Baehr RV, Ansorage S (1987) The role of dipeptidyl peptidase IV in human T lymphocyte activation. Inhibitors and antibodies against dipeptidyl peptidase IV suppresses lymphocyte proliferation and immunoglobulin synthesis in vitro. Eur J Immunol 17:18–21CrossRef
22.
go back to reference Turner AJ, Hooper NM, Kenny AJ (1987) Metabolism of neuropeptides in mammalian ectoenzymes (Research Monographs in Cell and Tissue Physiology). Kenny AJ, Turner AJ (eds) Elsevier, Amsterdam, pp 211–248 Turner AJ, Hooper NM, Kenny AJ (1987) Metabolism of neuropeptides in mammalian ectoenzymes (Research Monographs in Cell and Tissue Physiology). Kenny AJ, Turner AJ (eds) Elsevier, Amsterdam, pp 211–248
23.
go back to reference Terstappen LW, Loken MR (1990) Myeloid cell differentiation in non leukemic marrow and acute myeloid leukemia assessed by multi-dimensional flowcytometery. Anal Cell Pathol 2:229–240PubMed Terstappen LW, Loken MR (1990) Myeloid cell differentiation in non leukemic marrow and acute myeloid leukemia assessed by multi-dimensional flowcytometery. Anal Cell Pathol 2:229–240PubMed
24.
go back to reference UcKun FM (1990) Regulation of human B cell ontogeny. Blood 76:1908–1923PubMed UcKun FM (1990) Regulation of human B cell ontogeny. Blood 76:1908–1923PubMed
25.
go back to reference Vogel P, Erf LA (1937) Hematological observations on bone marrow obtained by sternal puncture. Am J Clin Pathol 7:436–447 Vogel P, Erf LA (1937) Hematological observations on bone marrow obtained by sternal puncture. Am J Clin Pathol 7:436–447
26.
go back to reference Wang LD, Clark MR (2003) B-cell antigen–receptor signaling in lymphocyte development. Immunology 110:411–420CrossRefPubMed Wang LD, Clark MR (2003) B-cell antigen–receptor signaling in lymphocyte development. Immunology 110:411–420CrossRefPubMed
Metadata
Title
Expression of CD13/aminopeptidase N in precursor B-cell leukemia: role in growth regulation of B cells
Authors
Ankit Saxena
Ambak Rai
Vinod Raina
Tulika Seth
Dipendra Kumar Mitra
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 1/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-009-0731-6

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