Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit A

 

 Buy Article Permissions and Reprints

Summary

Blood coagulation factor XIII (FXIII) is a protransglutaminase circulating asa tetramer formed by two types of subunits (A₂B₂). The intracellular dimeric form of FXIII (A₂) is present in platelets, megakaryocytes, monocytes and macrophages and has been detected in mono-and megakaryocytic leukemias. The aim of our study was to investigate FXIII-A expression in newly diagnosed B cell acute lymphoblastic leukemia (ALL) samples. We examined 47 de novo ALL cases of B cell origin by triple color labeling with flow cytometry. FXIII-A was detected by a FITC conjugated monoclonal antibody combined with CD34 and CD45 staining. In selected cases FXIII-A was investigated on slides prepared from blasts and visualized with a fluorescent microscope. In addition, blasts were studied by Western blot analysis and FXIII-A was measured by a highly sensitive ELISA method. By flow cytometry 19 samples of the 47 cases were found to be FXIII-A positive. Antigen concentration was 3.11± 1.19 fg/blast, while normal lymphoid precursors and mature lymphocytes from B-CLL did not contain FXIII-A. In the lysate of lymphoblasts that were positive by flow cytometry, a single band (82 kDa) corresponding to FXIII-A was detected on Western blots. Confocal laser scanning microscopic examination revealed the presence of FXIII-A in the cytoplasm of these lymphoblasts. This novel expression site of FXIII-A in leukemic lymphoblasts can be utilized as a diagnostic tool and may also gain functional significance in B-lineage ALL.

^* These authors contributed equally.

• References

• 1 Muszbek L, Ádány R, Mikkola H. Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function. Crit Rev Clin Lab Sci 1996; 33: 357-421.
  CrossrefPubMedGoogle Scholar
• 2 Muszbek L, Yee VC, Hevessy Z. Blood coagulation factor XIII: structure and function. Thromb Res 1999; 94: 271-305.
  CrossrefPubMedGoogle Scholar
• 3 Muszbek L, Ádány R, Szegedi G. et al. Factor XIII of blood coagulation in human monocytes. Thromb Res 1985; 37: 401-10.
  CrossrefPubMedGoogle Scholar
• 4 Henriksson P, Becker S, Lynch G. et al. Identification of intracellular factor XIII in human monocytes and macrophages. J Clin Invest 1985; 76: 528-34.
  CrossrefPubMedGoogle Scholar
• 5 Ádány R, Belkin A, Vasilevskaya T. et al. Identification of blood coagulation factor XIII in human peritoneal macrophages. Eur J Cell Biol 1985; 38: 171-3.
  PubMedGoogle Scholar
• 6 Kiesselbach TH, Wagner RH. Demonstration of factor XIII in human megakaryocytes by a fluorescent antibody technique. Ann NY Acad Sci 1972; 202: 318-28.
  CrossrefPubMedGoogle Scholar
• 7 Buluk K. An unknown function of blood platelets. Polski Tygod Lekar 1955; 10: 191-7.
  PubMedGoogle Scholar
• 8 Ádány R, Kiss A, Muszbek L. Factor XIII: a marker of mono-and megakaryocytopoiesis. Br J Haematol 1987; 67: 167-72.
  CrossrefPubMedGoogle Scholar
• 9 Kappelmayer J, Bacskó G, Birinyi L. et al. Consecutive appearance of coagulation factor XIII subunit A in macrophages, megakaryocytes and liver cells during early phase of human development. Blood 1995; 86: 2191-7.
  PubMedGoogle Scholar
• 10 Kappelmayer J, Simon A, Katona E. et al. Coagulation factor XIII-A. A flow cytometric intracellular marker in the classification of acute myeloid leukemias. Thromb Haemost 2005; 94: 454-9.
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Drexler HG, Thiel E, Ludwig WD. Review of the incidence and clinical relevance of myeloid antigenpositive acute lymphoblastic leukemia. Leukemia 1991; 05: 637-45.
  PubMedGoogle Scholar
• 12 Preti HA, Huh YO, O’Brien SM. et al. Myeloid markers in adult acute lymphoblastic leukemia. Correlations with patient and disease characteristics and with prognosis. Cancer 1995; 76: 1564-70.
  CrossrefPubMedGoogle Scholar
• 13 Lauria F, Raspadori D, Martinelli G. et al. Increased expression of myeloid antigen markers in adult acute lymphoblastic leukemia patients: diagnostic and prognostic implications. Br J Haematol 1994; 87: 286-92.
  CrossrefPubMedGoogle Scholar
• 14 Boldt DH, Kopecky KJ, Head D. et al. Expression of myeloid antigens by blast cells in acute lymphoblastic leukemia of adults. The Southwest Oncology Group Experience. Leukemia 1994; 08: 2118-26.
  PubMedGoogle Scholar
• 15 Orfao A, Ciudad J, López-Berges MC. et al. Acute lymphoblastic leukemia (ALL): detection of minimal residual disease (MRD) at flow cytometry. Leuk Lymphoma 1994; 13 (Suppl. 01) 87-90.
  CrossrefPubMedGoogle Scholar
• 16 Lucio P, Gaipa G, van Lochem EG. et al. BIOMED-I concerted action report: flow cytometric immunophenotyping of precursor B-ALL with standardized triple-stainings. BIOMED-1 concerted action investigation of minimal residual disease in acute leukemia: international standardization and clinical evaluation. Leukemia 2001; 15: 1185-92.
  CrossrefPubMedGoogle Scholar
• 17 McKenna RW, Washington LT, Aquino DB. et al. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood 2001; 98: 2498-507.
  CrossrefPubMedGoogle Scholar
• 18 Katona E, Ajzner E, Tóth K. et al. Enzyme linked immunosorbent assay (ELISA) for the determination of blood coagulation factor XIII A-subunit in plasma and in cell lysates. J Immunol Methods 2001; 258: 127-35.
  CrossrefPubMedGoogle Scholar
• 19 Bene MC, Castoldi G, Knapp W. et al. „Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL)”. Leukemia 1995; 09: 1783-6.
  PubMedGoogle Scholar
• 20 Buccheri V, Matutes E, Dyer MJS. et al. Lineage commitment in biphenotypic acute leukemia. Leukemia 1993; 07: 919-27.
  PubMedGoogle Scholar
• 21 Deptala A, Halicka HD, Salomon T. et al. Malignancy: A New Approach to the Analysis of Apoptosis in the Leukemic Subpopulation by Flow Cytometry Using a CD45 Gating Strategy. Hematology 1999; 04: 113-21.
  CrossrefPubMedGoogle Scholar
• 22 Lacombe F, Durrieu F, Briais A. et al. Flow cytometry CD45 gating for immunophenotyping of acute myeloid leukemia. Leukemia 1997; 11: 1878-86.
  CrossrefPubMedGoogle Scholar
• 23 Kappelmayer J, Gratama JW, Karaszi E. et al. Flow cytometric detection of intracellular myeloperoxidase, CD3 and CD79a. Interactions between monoclonal antibody clones, fluorochromes and sample preparation protocols. J Immunol Methods 2000; 242: 53-65.
  CrossrefPubMedGoogle Scholar
• 24 Invernizzi R, De Fazio P, Iannone AM. et al. Immunocytochemical detection of factor XIII A-subunit in acute leukemia. Leuk Res 1992; 16: 829-36.
  CrossrefPubMedGoogle Scholar
• 25 Campana D, Coustand-Smith E. Minimal residual disease studies by flow cytometry in acute leukemia. Acta Haematol 2004; 112: 8-15.
  CrossrefPubMedGoogle Scholar
• 26 Garcia JAVela, Monteserin MC, Delgado I. et al. Aberrant immunophenotypes detected by flow cytometry in acute lymphoblastic leukemia. Leuk Lymphoma 2000; 36: 275-84.
  CrossrefPubMedGoogle Scholar
• 27 Ádány R, Bárdos H, Antal M. et al. Factor XIII of blood coagulation as a nuclear crosslinking enzyme. Thromb Haemost 2001; 85: 845-51.
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 Sárváry A, Szûcs S, Balogh I. et al. Possible role of factor XIII subunit A in Fcgamma and complement receptor-mediated phagocytosis. Cell Immunol 2004; 228: 81-90.
  CrossrefPubMedGoogle Scholar
• 29 Törôcsik D, Bárdos H, Nagy L. et al. Identification of factor XIII-A as a marker of alternative macrophage activation. Cell Mol Life Sci 2005; 62: 2132-9.
  CrossrefPubMedGoogle Scholar
• 30 Dardik R, Loscalzo J, Eskaraev R. et al. Molecular mechanisms underlying the proangiogenic effect of factor XIII. Arterioscler Thromb Vasc Biol 2005; 25: 526-32.
  CrossrefPubMedGoogle Scholar