Abstract
Although the exact mechanism for the progression of myelofibrosis in acute megakaryoblastic leukaemia is unclear, certain humoral factors released from the proliferating megakaryoblasts that are unable to store these factors in their defective alpha-granules, including platelet derived growth factor (PDGF), fibroblast growth factors (FGF), platelet factor-4 (PF-4), transforming growth factor-beta (TGF-beta) and beta-thromboglobulin, could result in increased collagen synthesis by bone marrow fibroblasts. Recently, the human megakaryoblastic leukaemia cell line MEG-01 has been shown to produce both TGF-beta and PF-4 which have enhanced the growth of bone marrow fibroblasts. Therefore, we have examined the presence of a fibroblast growth stimulating activity and the humoral factors that might be responsible for it in the supernatant of the human megakaryoblastic leukaemia cell line ELF-153 recently established in our laboratory from a patient with acute myelofibrosis. A new fibroblast growth stimulating activity has been identified in the supernatant of the ELF-153 human megakaryoblastic leukaemia cell line that is independent of the percentage of fetal calf serum in NRK-49F fibroblast agar clonogenic assays and is not due to any of the known fibroblast growth stimulating humoral factors including PDGF, epithelial growth factor, TGF-alpha or beta, tumour necrosis factor-alpha, interleukin-1, 2, 4 or 6, FGF, fibronectin, PF-4 and factor VIII AG. Also, in vivo, subcutaneous injection of ELF-153 megakaryoblastic leukaemia cells into nude mice formed, in three out of the five mice after 6 weeks, subcutaneous tumours with a very rigid texture whose histological examination revealed dense infiltration by blast cells and pronounced reticular fibrosis. Immunohistochemistry demonstrated exclusive deposition of collagen III in the extracellular matrix whereas laminin and collagen IV were absent.(ABSTRACT TRUNCATED AT 250 WORDS)
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- Adachi M., Ryo R., Yoshida A., Yamaguchi N., Izumi Y. Refractory anemia terminating in acute megakaryoblastic leukemia (M7). Acta Haematol. 1989;81(2):104–108. doi: 10.1159/000205536. [DOI] [PubMed] [Google Scholar]
- Akahoshi M., Oshimi K., Mizoguchi H., Okada M., Enomoto Y., Watanabe Y. Myeloproliferative disorders terminating in acute megakaryoblastic leukemia with chromosome 3q26 abnormality. Cancer. 1987 Dec 1;60(11):2654–2661. doi: 10.1002/1097-0142(19871201)60:11<2654::aid-cncr2820601114>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
- Armstrong E., Vainikka S., Partanen J., Korhonen J., Alitalo R. Expression of fibroblast growth factor receptors in human leukemia cells. Cancer Res. 1992 Apr 1;52(7):2004–2007. [PubMed] [Google Scholar]
- Avraham H., Banu N., Scadden D. T., Abraham J., Groopman J. E. Modulation of megakaryocytopoiesis by human basic fibroblast growth factor. Blood. 1994 Apr 15;83(8):2126–2132. [PubMed] [Google Scholar]
- Bikfalvi A., Han Z. C. Angiogenic factors are hematopoietic growth factors and vice versa. Leukemia. 1994 Mar;8(3):523–529. [PubMed] [Google Scholar]
- Bikfalvi A., Han Z. C., Fuhrmann G. Interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis and demonstration of FGF receptor expression in megakaryocytes and megakaryocytic-like cells. Blood. 1992 Oct 15;80(8):1905–1913. [PubMed] [Google Scholar]
- Breton-Gorius J., Bizet M., Reyes F., Dupuy E., Mear C., Vannier J. P., Tron P. Myelofibrosis and acute megakaryoblastic leukemia in a child: topographic relationship between fibroblasts and megakaryocytes with an alpha-granule defect. Leuk Res. 1982;6(1):97–110. doi: 10.1016/0145-2126(82)90048-0. [DOI] [PubMed] [Google Scholar]
- Castro-Malaspina H., Rabellino E. M., Yen A., Nachman R. L., Moore M. A. Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts. Blood. 1981 Apr;57(4):781–787. [PubMed] [Google Scholar]
- Chan W. C., Brynes R. K., Kim T. H., Verras A., Schick C., Green R. J., Ragab A. H. Acute megakaryoblastic leukemia in early childhood. Blood. 1983 Jul;62(1):92–98. [PubMed] [Google Scholar]
- Donhuijsen-Ant R., Schadeck-Gressel C., Schmidt U., Löffler H., Westerhausen M., Leder L. D. Acute megakaryoblastic leukemia: a case report. Haematol Blood Transfus. 1990;33:362–367. doi: 10.1007/978-3-642-74643-7_69. [DOI] [PubMed] [Google Scholar]
- Gay S., Gay R. E., Prchal J. T. Immunohistological studies of bone marrow collagen. Prog Clin Biol Res. 1984;154:291–306. [PubMed] [Google Scholar]
- Guba S. C., Sartor C. I., Gottschalk L. R., Jing Y. H., Mulligan T., Emerson S. G. Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte-macrophage colony-stimulating factor in the absence of inflammatory stimulation: demonstration by serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction. Blood. 1992 Sep 1;80(5):1190–1198. [PubMed] [Google Scholar]
- Han Z. C., Bellucci S., Wan H. Y., Caen J. P. New insights into the regulation of megakaryocytopoiesis by haematopoietic and fibroblastic growth factors and transforming growth factor beta 1. Br J Haematol. 1992 May;81(1):1–5. doi: 10.1111/j.1365-2141.1992.tb08161.x. [DOI] [PubMed] [Google Scholar]
- Hassan H. T., Grell S., Borrmann-Danso U., Freund M. Effect of recombinant human interferons in inducing differentiation of acute megakaryoblastic leukaemia blast cells. Leuk Lymphoma. 1995 Jan;16(3-4):329–333. doi: 10.3109/10428199509049772. [DOI] [PubMed] [Google Scholar]
- Hassan H. T., Grell S., Borrmann-Danso U., Freund M. Interleukin-4 inhibits proliferation of human leukemic megakaryoblast cell line MHH 225. Hematol Oncol. 1994 Mar-Apr;12(2):61–66. doi: 10.1002/hon.2900120203. [DOI] [PubMed] [Google Scholar]
- Hoshikawa N., Shirasawa K., Niino H., Hasegawa N., Fukuzumi N. Acute leukemia of megakaryocyte lineage with tumor formation. An autopsy case of patient with Down's syndrome. Acta Pathol Jpn. 1988 Feb;38(2):193–207. doi: 10.1111/j.1440-1827.1988.tb01097.x. [DOI] [PubMed] [Google Scholar]
- Huang M. J., Li C. Y., Nichols W. L., Young J. H., Katzmann J. A. Acute leukemia with megakaryocytic differentiation: a study of 12 cases identified immunocytochemically. Blood. 1984 Aug;64(2):427–439. [PubMed] [Google Scholar]
- Kaplan D. R., Chao F. C., Stiles C. D., Antoniades H. N., Scher C. D. Platelet alpha granules contain a growth factor for fibroblasts. Blood. 1979 Jun;53(6):1043–1052. [PubMed] [Google Scholar]
- Manoharan A. Annotation. Myelofibrosis: prognostic factors and treatment. Br J Haematol. 1988 Jul;69(3):295–298. doi: 10.1111/j.1365-2141.1988.tb02365.x. [DOI] [PubMed] [Google Scholar]
- Mouthon M. A., Freund M., Titeux M., Katz A., Guichard J., Breton-Gorius J., Vainchenker W. Growth and differentiation of the human megakaryoblastic cell line (ELF-153): a model for early stages of megakaryocytopoiesis. Blood. 1994 Aug 15;84(4):1085–1097. [PubMed] [Google Scholar]
- Palomera Bernal L., García Díez I. Betatromboglobulina y factor 4 plaquetario en el seguimiento de una mielofibrosis aguda (leucemia megacarioblástica). Med Clin (Barc) 1990 Jun 2;95(1):21–24. [PubMed] [Google Scholar]
- Papayannopoulou T., Raines E., Collins S., Nakamoto B., Tweeddale M., Ross R. Constitutive and inducible secretion of platelet-derived growth factor analogs by human leukemic cell lines coexpressing erythroid and megakaryocytic markers. J Clin Invest. 1987 Mar;79(3):859–866. doi: 10.1172/JCI112895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reilly J. T. Pathogenesis of idiopathic myelofibrosis: role of growth factors. J Clin Pathol. 1992 Jun;45(6):461–464. doi: 10.1136/jcp.45.6.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tanabe N., Tanaka M., Ogura M., Morishita Y., Takamatu J., Saito H. The effect of low affinity platelet factor 4 (LAPF4) secreted by human megakaryoblastic cell line (MEG-01) upon human bone marrow fibroblasts. Haematologica. 1991 May-Jun;76(3):193–199. [PubMed] [Google Scholar]
- Terui T., Niitsu Y., Mahara K., Fujisaki Y., Urushizaki Y., Mogi Y., Kohgo Y., Watanabe N., Ogura M., Saito H. The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis. Blood. 1990 Apr 1;75(7):1540–1548. [PubMed] [Google Scholar]
- Washio S., Ido M., Azuma E., Fukui M., Shibata T., Zhang S. L., Komada Y., Ito M., Koike T., Kaneko Y. Acute megakaryoblastic leukemia with translocation t(1;22)(p13;q13) in a 10-week-old infant. Am J Hematol. 1992 Jan;39(1):56–60. doi: 10.1002/ajh.2830390112. [DOI] [PubMed] [Google Scholar]
- Weisenburger D. D. Acute myelofibrosis terminating as acute myeloblastic leukemia. Am J Clin Pathol. 1980 Jan;73(1):128–132. doi: 10.1093/ajcp/73.1.128. [DOI] [PubMed] [Google Scholar]
- Winkelmann M., Aul C., Scharf R. E., Schmitt-Gräff A., Carbonell F., Villeval J. L., Grosse-Wilde H., Fischer J. T., Schneider W. Acute myelofibrosis in megakaryoblastic leukemia with translocation between chromosomes 8 and 14. Klin Wochenschr. 1987 Nov 2;65(21):1034–1041. doi: 10.1007/BF01726322. [DOI] [PubMed] [Google Scholar]
- Yasunaga M., Ryo R., Sugano W., Yamaguchi N. Detection of platelet-specific protein mRNAs in different megakaryoblasts using the reverse transcriptase polymerase chain reaction. Leuk Lymphoma. 1992 Aug;7(5-6):505–510. doi: 10.3109/10428199209049808. [DOI] [PubMed] [Google Scholar]
- den Ottolander G. J., te Velde J., Brederoo P., Geraedts J. P., Slee P. H., Willemze R., Zwaan F. E., Haak H. L., Muller H. P., Bieger R. Megakaryoblastic leukaemia (acute myelofibrosis): a report of three cases. Br J Haematol. 1979 May;42(1):9–20. doi: 10.1111/j.1365-2141.1979.tb03693.x. [DOI] [PubMed] [Google Scholar]


