Skip to main content
Erschienen in: Annals of Hematology 11/2018

30.06.2018 | Original Article

Profile of fibrosis-related gene transcripts and megakaryocytic changes in the bone marrow of myelodysplastic syndromes with fibrosis

verfasst von: Kais Hussein, Angelika Stucki-Koch, Hans Kreipe

Erschienen in: Annals of Hematology | Ausgabe 11/2018

Einloggen, um Zugang zu erhalten

Abstract

Bone marrow fibrosis (MF) in myelodysplastic syndromes (MDS) is associated with an adverse prognosis. It is likely that molecular changes similar to those in primary myelofibrosis (PMF) lead to MDS-MF, but gene expression profiling has not yet been carried out. We analysed bone marrow biopsy samples by PCR, qPCR (45 transcripts per sample), and immunohistochemistry from MDS patients with fibrosis (n = 70/119; including 19/70 MF0 > MF follow-up cases), MDS without fibrosis (n = 49/119), and 33 controls. SRSF2 and JAK2 mutations were detectable in up to 13% including 3/19 follow-up cases with evidence of clonal evolution during MF progression. MDS-MF showed increased expression of thrombospondin 1 (THBS1), TIMP metallopeptidase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGFB1), matrix metallopeptidases 2 and 14 (MMP2, MMP14), SMAD family members 3 and 4 (SMAD3, SMAD4), and miR-146b. Paralleling MF progression, a subfraction of follow-up cases showed megakaryocytic changes with increased CD42b+ pro-platelet deposition in the bone marrow. In summary, fibrosis in MDS-MF and PMF shows many molecular and morphological similarities.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Ramos F, Robledo C, Izquierdo-García FM, Suárez-Vilela D, Benito R, Fuertes M, Insunza A, Barragán E, del Rey M, García-Ruiz de Morales JM, Tormo M, Salido E, Zamora L, Pedro C, Sánchez-del-Real J, Díez-Campelo M, del Cañizo C, Sanz GF, Hernández-Rivas JM, Spanish Group for Myelodysplastic Syndromes (GESMD) (2016) Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis. Oncotarget 7:30492–30503CrossRef Ramos F, Robledo C, Izquierdo-García FM, Suárez-Vilela D, Benito R, Fuertes M, Insunza A, Barragán E, del Rey M, García-Ruiz de Morales JM, Tormo M, Salido E, Zamora L, Pedro C, Sánchez-del-Real J, Díez-Campelo M, del Cañizo C, Sanz GF, Hernández-Rivas JM, Spanish Group for Myelodysplastic Syndromes (GESMD) (2016) Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis. Oncotarget 7:30492–30503CrossRef
2.
Zurück zum Zitat Machherndl-Spandl S, Sega W, Bösmüller H, Germing U, Gruber C, Nachtkamp K, Reinecke P, Sperr WR, Wimazal F, Müllauer L, Sotlar K, Horny HP, Tüchler H, Valent P, Krieger O (2014) Prognostic impact of blast cell counts in dysplastic bone marrow disorders (MDS and CMML I) with concomitant fibrosis. Ann Hematol 93:57–64CrossRef Machherndl-Spandl S, Sega W, Bösmüller H, Germing U, Gruber C, Nachtkamp K, Reinecke P, Sperr WR, Wimazal F, Müllauer L, Sotlar K, Horny HP, Tüchler H, Valent P, Krieger O (2014) Prognostic impact of blast cell counts in dysplastic bone marrow disorders (MDS and CMML I) with concomitant fibrosis. Ann Hematol 93:57–64CrossRef
3.
Zurück zum Zitat Fu B, Ok CY, Goswami M, Xei W, Jaso JM, Muzzafar T, Bueso-Ramos C, Verstovsek S, Garcia-Manero G, Medeiros LJ, Wang SA (2013) The clinical importance of moderate/severe bone marrow fibrosis in patients with therapy-related myelodysplastic syndromes. Ann Hematol 92:1335–1343CrossRef Fu B, Ok CY, Goswami M, Xei W, Jaso JM, Muzzafar T, Bueso-Ramos C, Verstovsek S, Garcia-Manero G, Medeiros LJ, Wang SA (2013) The clinical importance of moderate/severe bone marrow fibrosis in patients with therapy-related myelodysplastic syndromes. Ann Hematol 92:1335–1343CrossRef
4.
Zurück zum Zitat Kröger N, Zabelina T, van Biezen A, Brand R, Niederwieser D, Martino R et al (2011) Allogeneic stem cell transplantation for myelodysplastic syndromes with bone marrow fibrosis. Haematologica 96:291–297CrossRef Kröger N, Zabelina T, van Biezen A, Brand R, Niederwieser D, Martino R et al (2011) Allogeneic stem cell transplantation for myelodysplastic syndromes with bone marrow fibrosis. Haematologica 96:291–297CrossRef
5.
Zurück zum Zitat Della Porta MG, Malcovati L, Boveri E, Travaglino E, Pietra D, Pascutto C, Passamonti F, Invernizzi R, Castello A, Magrini U, Lazzarino M, Cazzola M (2009) Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol 27:754–762CrossRef Della Porta MG, Malcovati L, Boveri E, Travaglino E, Pietra D, Pascutto C, Passamonti F, Invernizzi R, Castello A, Magrini U, Lazzarino M, Cazzola M (2009) Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol 27:754–762CrossRef
6.
Zurück zum Zitat Buesche G, Teoman H, Wilczak W, Ganser A, Hecker H, Wilkens L, Göhring G, Schlegelberger B, Bock O, Georgii A, Kreipe H (2008) Marrow fibrosis predicts early fatal marrow failure in patients with myelodysplastic syndromes. Leukemia 22:313–322CrossRef Buesche G, Teoman H, Wilczak W, Ganser A, Hecker H, Wilkens L, Göhring G, Schlegelberger B, Bock O, Georgii A, Kreipe H (2008) Marrow fibrosis predicts early fatal marrow failure in patients with myelodysplastic syndromes. Leukemia 22:313–322CrossRef
7.
Zurück zum Zitat Scott BL, Storer BE, Greene JE, Hackman RC, Appelbaum FR, Deeg HJ (2007) Marrow fibrosis as a risk factor for posttransplantation outcome in patients with advanced myelodysplastic syndrome or acute myeloid leukemia with multilineage dysplasia. Biol Blood Marrow Transplant 13:345–354CrossRef Scott BL, Storer BE, Greene JE, Hackman RC, Appelbaum FR, Deeg HJ (2007) Marrow fibrosis as a risk factor for posttransplantation outcome in patients with advanced myelodysplastic syndrome or acute myeloid leukemia with multilineage dysplasia. Biol Blood Marrow Transplant 13:345–354CrossRef
8.
Zurück zum Zitat Mondet J, Hussein K, Mossuz P (2015) Circulating cytokine levels as markers of inflammation in Philadelphia negative myeloproliferative neoplasms: diagnostic and prognostic interest. Mediat Inflamm 2015:670580CrossRef Mondet J, Hussein K, Mossuz P (2015) Circulating cytokine levels as markers of inflammation in Philadelphia negative myeloproliferative neoplasms: diagnostic and prognostic interest. Mediat Inflamm 2015:670580CrossRef
9.
Zurück zum Zitat Kvasnicka HM, Beham-Schmid C, Bob R, Dirnhofer S, Hussein K, Kreipe H, Kremer M, Schmitt-Graeff A, Schwarz S, Thiele J, Werner M, Stein H (2016) Problems and pitfalls in grading of bone marrow fibrosis, collagen deposition and osteosclerosis—a consensus-based study. Histopathology 68:905–915CrossRef Kvasnicka HM, Beham-Schmid C, Bob R, Dirnhofer S, Hussein K, Kreipe H, Kremer M, Schmitt-Graeff A, Schwarz S, Thiele J, Werner M, Stein H (2016) Problems and pitfalls in grading of bone marrow fibrosis, collagen deposition and osteosclerosis—a consensus-based study. Histopathology 68:905–915CrossRef
10.
Zurück zum Zitat Gangat N, Patnaik MM, Tefferi A (2016) Myelodysplastic syndromes: contemporary review and how we treat. Am J Hematol 91:76–89CrossRef Gangat N, Patnaik MM, Tefferi A (2016) Myelodysplastic syndromes: contemporary review and how we treat. Am J Hematol 91:76–89CrossRef
11.
Zurück zum Zitat Sochacki AL, Fischer MA, Savona MR (2016) Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes. Onco Targets Ther 9:2273–2286PubMedPubMedCentral Sochacki AL, Fischer MA, Savona MR (2016) Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes. Onco Targets Ther 9:2273–2286PubMedPubMedCentral
12.
Zurück zum Zitat Lehmann U, Bartels S, Hasemeier B, Geffers R, Schlue J, Büsche G et al (2013) SRSF2 mutation is present in the hypercellular and prefibrotic stage of primary myelofibrosis. Blood 121:4011–4012CrossRef Lehmann U, Bartels S, Hasemeier B, Geffers R, Schlue J, Büsche G et al (2013) SRSF2 mutation is present in the hypercellular and prefibrotic stage of primary myelofibrosis. Blood 121:4011–4012CrossRef
13.
Zurück zum Zitat Hussein K, Stucki-Koch A, Göhring G, Kreipe H, Suttorp M (2017) Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukaemia with bone marrow fibrosis. Leukemia 31:1540–1546CrossRef Hussein K, Stucki-Koch A, Göhring G, Kreipe H, Suttorp M (2017) Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukaemia with bone marrow fibrosis. Leukemia 31:1540–1546CrossRef
14.
Zurück zum Zitat Hussein K, Stucki-Koch A, Alchalby H, Triviai I, Kröger N, Kreipe H (2016) Cytokine expression pattern in bone marrow microenvironment after allogeneic stem cell transplantation in primary myelofibrosis. Biol Blood Marrow Transplant 22:644–650CrossRef Hussein K, Stucki-Koch A, Alchalby H, Triviai I, Kröger N, Kreipe H (2016) Cytokine expression pattern in bone marrow microenvironment after allogeneic stem cell transplantation in primary myelofibrosis. Biol Blood Marrow Transplant 22:644–650CrossRef
15.
Zurück zum Zitat Hussein K, Theophile K, Büsche G, Schlegelberger B, Göhring G, Kreipe H, Bock O (2010) Aberrant microRNA expression pattern in myelodysplastic bone marrow cells. Leuk Res 34:1169–1174CrossRef Hussein K, Theophile K, Büsche G, Schlegelberger B, Göhring G, Kreipe H, Bock O (2010) Aberrant microRNA expression pattern in myelodysplastic bone marrow cells. Leuk Res 34:1169–1174CrossRef
16.
Zurück zum Zitat Muth M, Büsche G, Bock O, Hussein K, Kreipe H (2010) Aberrant proplatelet formation in chronic myeloproliferative neoplasms. Leuk Res 34:1424–1429CrossRef Muth M, Büsche G, Bock O, Hussein K, Kreipe H (2010) Aberrant proplatelet formation in chronic myeloproliferative neoplasms. Leuk Res 34:1424–1429CrossRef
17.
Zurück zum Zitat Muth M, Engelhardt BM, Kröger N, Hussein K, Schlué J, Büsche G, Kreipe HH, Bock O (2011) Thrombospondin-1 (TSP-1) in primary myelofibrosis (PMF)—a megakaryocyte-derived biomarker which largely discriminates PMF from essential thrombocythemia. Ann Hematol 90:33–40CrossRef Muth M, Engelhardt BM, Kröger N, Hussein K, Schlué J, Büsche G, Kreipe HH, Bock O (2011) Thrombospondin-1 (TSP-1) in primary myelofibrosis (PMF)—a megakaryocyte-derived biomarker which largely discriminates PMF from essential thrombocythemia. Ann Hematol 90:33–40CrossRef
18.
Zurück zum Zitat Jonigk D, Theophile K, Hussein K, Bock O, Lehmann U, Bockmeyer CL, Gottlieb J, Fischer S, Simon A, Welte T, Maegel L, Kreipe H, Laenger F (2010) Obliterative airway remodelling in transplanted and non-transplanted lungs. Virchows Arch 457:369–380CrossRef Jonigk D, Theophile K, Hussein K, Bock O, Lehmann U, Bockmeyer CL, Gottlieb J, Fischer S, Simon A, Welte T, Maegel L, Kreipe H, Laenger F (2010) Obliterative airway remodelling in transplanted and non-transplanted lungs. Virchows Arch 457:369–380CrossRef
19.
Zurück zum Zitat Stucki-Koch A, Hauck G, Kreipe H, Hussein K (2015) MicroRNA expression profiles in BCR-ABL-negative primary myelofibrosis with chromosome 7q defects. J Hematop 8:203–208CrossRef Stucki-Koch A, Hauck G, Kreipe H, Hussein K (2015) MicroRNA expression profiles in BCR-ABL-negative primary myelofibrosis with chromosome 7q defects. J Hematop 8:203–208CrossRef
20.
Zurück zum Zitat Bock O, Muth M, Theophile K, Winter M, Hussein K, Büsche G, Kröger N, Kreipe H (2009) Identification of new target molecules PTK2, TGFBR2 and CD9 overexpressed during advanced bone marrow remodelling in primary myelofibrosis. Br J Haematol 146:510–520CrossRef Bock O, Muth M, Theophile K, Winter M, Hussein K, Büsche G, Kröger N, Kreipe H (2009) Identification of new target molecules PTK2, TGFBR2 and CD9 overexpressed during advanced bone marrow remodelling in primary myelofibrosis. Br J Haematol 146:510–520CrossRef
21.
Zurück zum Zitat Bock O, Höftmann J, Theophile K, Hussein K, Wiese B, Schlué J, Kreipe H (2008) Bone morphogenetic proteins are overexpressed in the bone marrow of primary myelofibrosis and are apparently induced by fibrogenic cytokines. Am J Pathol 172:951–960CrossRef Bock O, Höftmann J, Theophile K, Hussein K, Wiese B, Schlué J, Kreipe H (2008) Bone morphogenetic proteins are overexpressed in the bone marrow of primary myelofibrosis and are apparently induced by fibrogenic cytokines. Am J Pathol 172:951–960CrossRef
22.
Zurück zum Zitat Loghavi S, Al-Ibraheemi A, Zuo Z, Garcia-Manero G, Yabe M, Wang SA et al (2015) TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis. Br J Haematol 171:91–99CrossRef Loghavi S, Al-Ibraheemi A, Zuo Z, Garcia-Manero G, Yabe M, Wang SA et al (2015) TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis. Br J Haematol 171:91–99CrossRef
23.
Zurück zum Zitat Bektas O, Uner A, Buyukasik Y, Uz B, Bozkurt S, Eliacik E, Işik A, Haznedaroglu IC, Goker H, Demiroglu H, Aksu S, Ozcebe OI, Sayinalp N (2015) Clinical and pathological correlations of marrow PUMA and P53 expressions in myelodysplastic syndromes. APMIS 123:445–451CrossRef Bektas O, Uner A, Buyukasik Y, Uz B, Bozkurt S, Eliacik E, Işik A, Haznedaroglu IC, Goker H, Demiroglu H, Aksu S, Ozcebe OI, Sayinalp N (2015) Clinical and pathological correlations of marrow PUMA and P53 expressions in myelodysplastic syndromes. APMIS 123:445–451CrossRef
24.
Zurück zum Zitat Yang L, Qian Y, Eksioglu E, Epling-Burnette PK, Wei S (2015) The inflammatory microenvironment in MDS. Cell Mol Life Sci 72:1959–1966CrossRef Yang L, Qian Y, Eksioglu E, Epling-Burnette PK, Wei S (2015) The inflammatory microenvironment in MDS. Cell Mol Life Sci 72:1959–1966CrossRef
25.
Zurück zum Zitat Kittang AO, Sand K, Brenner AK, Rye KP, Bruserud Ø (2016) The systemic profile of soluble immune mediators in patients with myelodysplastic syndromes. Int J Mol Sci 17:E1080CrossRef Kittang AO, Sand K, Brenner AK, Rye KP, Bruserud Ø (2016) The systemic profile of soluble immune mediators in patients with myelodysplastic syndromes. Int J Mol Sci 17:E1080CrossRef
26.
Zurück zum Zitat Ha JS, Jung HR (2015) Up-regulation of MicroRNA 146b is associated with myelofibrosis in myeloproliferative neoplasms. Ann Clin Lab Sci 45:308–314PubMed Ha JS, Jung HR (2015) Up-regulation of MicroRNA 146b is associated with myelofibrosis in myeloproliferative neoplasms. Ann Clin Lab Sci 45:308–314PubMed
27.
Zurück zum Zitat Hussein K, Theophile K, Dralle W, Wiese B, Kreipe H, Bock O (2009) MicroRNA expression profiling of megakaryocytes in primary myelofibrosis and essential thrombocythemia. Platelets 20:391–400CrossRef Hussein K, Theophile K, Dralle W, Wiese B, Kreipe H, Bock O (2009) MicroRNA expression profiling of megakaryocytes in primary myelofibrosis and essential thrombocythemia. Platelets 20:391–400CrossRef
28.
Zurück zum Zitat Paterson MR, Kriegel AJ (2017) MiR-146a/b: a family with shared seeds and different roots. Physiol Genomics 49:243–252CrossRef Paterson MR, Kriegel AJ (2017) MiR-146a/b: a family with shared seeds and different roots. Physiol Genomics 49:243–252CrossRef
29.
Zurück zum Zitat Curtale G, Mirolo M, Renzi TA, Rossato M, Bazzoni F, Locati M (2013) Negative regulation of Toll-like receptor 4 signaling by IL-10-dependent microRNA-146b. Proc Natl Acad Sci U S A 110:11499–11504CrossRef Curtale G, Mirolo M, Renzi TA, Rossato M, Bazzoni F, Locati M (2013) Negative regulation of Toll-like receptor 4 signaling by IL-10-dependent microRNA-146b. Proc Natl Acad Sci U S A 110:11499–11504CrossRef
30.
Zurück zum Zitat Budi EH, Duan D, Derynck R (2017) Transforming growth factor-β receptors and Smads: regulatory complexity and functional versatility. Trends Cell Biol 27:658–672CrossRef Budi EH, Duan D, Derynck R (2017) Transforming growth factor-β receptors and Smads: regulatory complexity and functional versatility. Trends Cell Biol 27:658–672CrossRef
31.
Zurück zum Zitat Kim MJ, Park SY, Chang HR, Jung EY, Munkhjargal A, Lim JS, Lee MS, Kim Y (2017) Clinical significance linked to functional defects in bone morphogenetic protein type 2 receptor, BMPR2. BMB Rep 50:308–317CrossRef Kim MJ, Park SY, Chang HR, Jung EY, Munkhjargal A, Lim JS, Lee MS, Kim Y (2017) Clinical significance linked to functional defects in bone morphogenetic protein type 2 receptor, BMPR2. BMB Rep 50:308–317CrossRef
32.
Zurück zum Zitat Akiyama T, Matsunaga T, Terui T, Miyanishi K, Tanaka I, Sato T, Kuroda H, Takimoto R, Takayama T, Kato J, Yamauchi N, Kogawa K, Sakamaki S, Hirayama Y, Kohda K, Niitsu Y (2005) Involvement of transforming growth factor-beta and thrombopoietin in the pathogenesis of myelodysplastic syndrome with myelofibrosis. Leukemia 19:1558–1566CrossRef Akiyama T, Matsunaga T, Terui T, Miyanishi K, Tanaka I, Sato T, Kuroda H, Takimoto R, Takayama T, Kato J, Yamauchi N, Kogawa K, Sakamaki S, Hirayama Y, Kohda K, Niitsu Y (2005) Involvement of transforming growth factor-beta and thrombopoietin in the pathogenesis of myelodysplastic syndrome with myelofibrosis. Leukemia 19:1558–1566CrossRef
33.
Zurück zum Zitat Bock O, Loch G, Schade U, von Wasielewski R, Schlué J, Kreipe H (2005) Aberrant expression of transforming growth factor beta-1 (TGF beta-1) per se does not discriminate fibrotic from non-fibrotic chronic myeloproliferative disorders. J Pathol 205:548–557CrossRef Bock O, Loch G, Schade U, von Wasielewski R, Schlué J, Kreipe H (2005) Aberrant expression of transforming growth factor beta-1 (TGF beta-1) per se does not discriminate fibrotic from non-fibrotic chronic myeloproliferative disorders. J Pathol 205:548–557CrossRef
34.
Zurück zum Zitat Åström M, Hahn-Strömberg V, Zetterberg E, Vedin I, Merup M, Palmblad J (2015) X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis. Am J Hematol 90:E44–E48CrossRef Åström M, Hahn-Strömberg V, Zetterberg E, Vedin I, Merup M, Palmblad J (2015) X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis. Am J Hematol 90:E44–E48CrossRef
35.
Zurück zum Zitat Niino D, Tsuchiya T, Tomonaga M, Miyazaki Y, Ohshima K (2013) Clinicopathological features of acute megakaryoblastic leukaemia: relationship between fibrosis and platelet-derived growth factor. Pathol Int 63:141–149CrossRef Niino D, Tsuchiya T, Tomonaga M, Miyazaki Y, Ohshima K (2013) Clinicopathological features of acute megakaryoblastic leukaemia: relationship between fibrosis and platelet-derived growth factor. Pathol Int 63:141–149CrossRef
36.
Zurück zum Zitat Machlus KR, Johnson KE, Kulenthirarajan R, Forward JA, Tippy MD, Soussou TS, el-Husayni SH, Wu SK, Wang S, Watnick RS, Italiano JE, Battinelli EM (2016) CCL5 derived from platelets increases megakaryocyte proplatelet formation. Blood 127:921–926CrossRef Machlus KR, Johnson KE, Kulenthirarajan R, Forward JA, Tippy MD, Soussou TS, el-Husayni SH, Wu SK, Wang S, Watnick RS, Italiano JE, Battinelli EM (2016) CCL5 derived from platelets increases megakaryocyte proplatelet formation. Blood 127:921–926CrossRef
37.
Zurück zum Zitat Garimella R, Kacena MA, Tague SE, Wang J, Horowitz MC, Anderson HC (2007) Expression of bone morphogenetic proteins and their receptors in the bone marrow megakaryocytes of GATA-1(low) mice: a possible role in osteosclerosis. J Histochem Cytochem 55:745–752CrossRef Garimella R, Kacena MA, Tague SE, Wang J, Horowitz MC, Anderson HC (2007) Expression of bone morphogenetic proteins and their receptors in the bone marrow megakaryocytes of GATA-1(low) mice: a possible role in osteosclerosis. J Histochem Cytochem 55:745–752CrossRef
38.
Zurück zum Zitat Bock O, Neuse J, Hussein K, Brakensiek K, Buesche G, Buhr T, Wiese B, Kreipe H (2006) Aberrant collagenase expression in chronic idiopathic myelofibrosis is related to the stage of disease but not to the JAK2 mutation status. Am J Pathol 169:471–481CrossRef Bock O, Neuse J, Hussein K, Brakensiek K, Buesche G, Buhr T, Wiese B, Kreipe H (2006) Aberrant collagenase expression in chronic idiopathic myelofibrosis is related to the stage of disease but not to the JAK2 mutation status. Am J Pathol 169:471–481CrossRef
39.
Zurück zum Zitat Eliades A, Papadantonakis N, Bhupatiraju A, Burridge KA, Johnston-Cox HA, Migliaccio AR, Crispino JD, Lucero HA, Trackman PC, Ravid K (2011) Control of megakaryocyte expansion and bone marrow fibrosis by lysyl oxidase. J Biol Chem 286:27630–27638CrossRef Eliades A, Papadantonakis N, Bhupatiraju A, Burridge KA, Johnston-Cox HA, Migliaccio AR, Crispino JD, Lucero HA, Trackman PC, Ravid K (2011) Control of megakaryocyte expansion and bone marrow fibrosis by lysyl oxidase. J Biol Chem 286:27630–27638CrossRef
40.
Zurück zum Zitat Nakayama S, Yokote T, Hiraoka N, Akioka T, Nishiwaki U, Miyoshi T, Iwaki K, Fumimoto A, Masuda Y, Hatooka J, Fujimoto M, Nishimura Y, Tsuji M (2017) Transforming growth factor β- and interleukin 13-producing mast cells are associated with fibrosis in bone marrow. Hum Pathol 62:180–186CrossRef Nakayama S, Yokote T, Hiraoka N, Akioka T, Nishiwaki U, Miyoshi T, Iwaki K, Fumimoto A, Masuda Y, Hatooka J, Fujimoto M, Nishimura Y, Tsuji M (2017) Transforming growth factor β- and interleukin 13-producing mast cells are associated with fibrosis in bone marrow. Hum Pathol 62:180–186CrossRef
41.
Zurück zum Zitat Battula VL, Chen Y, Cabreira Mda G, Ruvolo V, Wang Z, Ma W et al (2013) Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment. Blood 122:357–366CrossRef Battula VL, Chen Y, Cabreira Mda G, Ruvolo V, Wang Z, Ma W et al (2013) Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment. Blood 122:357–366CrossRef
42.
Zurück zum Zitat Tamura S, Suzuki-Inoue K, Tsukiji N, Shirai T, Sasaki T, Osada M, Satoh K, Ozaki Y (2016) Podoplanin-positive periarteriolar stromal cells promote megakaryocyte growth and proplatelet formation in mice by CLEC-2. Blood 127:1701–1710CrossRef Tamura S, Suzuki-Inoue K, Tsukiji N, Shirai T, Sasaki T, Osada M, Satoh K, Ozaki Y (2016) Podoplanin-positive periarteriolar stromal cells promote megakaryocyte growth and proplatelet formation in mice by CLEC-2. Blood 127:1701–1710CrossRef
43.
Zurück zum Zitat Yanase M, Ikeda H, Ogata I, Matsui A, Noiri E, Tomiya T, Arai M, Inoue Y, Tejima K, Nagashima K, Nishikawa T, Shibata M, Ikebe M, Rojkind M, Fujiwara K (2003) Functional diversity between Rho-kinase- and MLCK-mediated cytoskeletal actions in a myofibroblast-like hepatic stellate cell line. Biochem Biophys Res Commun 305:223–228CrossRef Yanase M, Ikeda H, Ogata I, Matsui A, Noiri E, Tomiya T, Arai M, Inoue Y, Tejima K, Nagashima K, Nishikawa T, Shibata M, Ikebe M, Rojkind M, Fujiwara K (2003) Functional diversity between Rho-kinase- and MLCK-mediated cytoskeletal actions in a myofibroblast-like hepatic stellate cell line. Biochem Biophys Res Commun 305:223–228CrossRef
44.
Zurück zum Zitat Meinders M, Kulu DI, van de Werken HJ, Hoogenboezem M, Janssen H, Brouwer RW et al (2015) Sp1/Sp3 transcription factors regulate hallmarks of megakaryocyte maturation and platelet formation and function. Blood 125:1957–1967CrossRef Meinders M, Kulu DI, van de Werken HJ, Hoogenboezem M, Janssen H, Brouwer RW et al (2015) Sp1/Sp3 transcription factors regulate hallmarks of megakaryocyte maturation and platelet formation and function. Blood 125:1957–1967CrossRef
45.
Zurück zum Zitat Travaglino E, Benatti C, Malcovati L, Della Porta MG, Gallì A, Bonetti E et al (2008) Biological and clinical relevance of matrix metalloproteinases 2 and 9 in acute myeloid leukaemias and myelodysplastic syndromes. Eur J Haematol 80:216–226CrossRef Travaglino E, Benatti C, Malcovati L, Della Porta MG, Gallì A, Bonetti E et al (2008) Biological and clinical relevance of matrix metalloproteinases 2 and 9 in acute myeloid leukaemias and myelodysplastic syndromes. Eur J Haematol 80:216–226CrossRef
46.
Zurück zum Zitat Lekovic D, Gotic M, Skoda R, Beleslin-Cokic B, Milic N, Mitrovic-Ajtic O, Nienhold R, Sefer D, Suboticki T, Buac M, Markovic D, Diklic M, Cokic VP (2017) Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations. Ann Hematol 96:393–404CrossRef Lekovic D, Gotic M, Skoda R, Beleslin-Cokic B, Milic N, Mitrovic-Ajtic O, Nienhold R, Sefer D, Suboticki T, Buac M, Markovic D, Diklic M, Cokic VP (2017) Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations. Ann Hematol 96:393–404CrossRef
47.
Zurück zum Zitat Pruneri G, Bertolini F, Soligo D, Carboni N, Cortelezzi A, Ferrucci PF, Buffa R, Lambertenghi-Deliliers G, Pezzella F (1999) Angiogenesis in myelodysplastic syndromes. Br J Cancer 81:1398–1401CrossRef Pruneri G, Bertolini F, Soligo D, Carboni N, Cortelezzi A, Ferrucci PF, Buffa R, Lambertenghi-Deliliers G, Pezzella F (1999) Angiogenesis in myelodysplastic syndromes. Br J Cancer 81:1398–1401CrossRef
48.
Zurück zum Zitat Babarović E, Valković T, Štifter S, Budisavljević I, Seili-Bekafigo I, Duletić-Načinović A, Lučin K, Jonjić N (2012) Assessment of bone marrow fibrosis and angiogenesis in monitoring patients with multiple myeloma. Am J Clin Pathol 137:870–878CrossRef Babarović E, Valković T, Štifter S, Budisavljević I, Seili-Bekafigo I, Duletić-Načinović A, Lučin K, Jonjić N (2012) Assessment of bone marrow fibrosis and angiogenesis in monitoring patients with multiple myeloma. Am J Clin Pathol 137:870–878CrossRef
49.
Zurück zum Zitat Eklund L, Kangas J, Saharinen P (2017) Angiopoietin-Tie signalling in the cardiovascular and lymphatic systems. Clin Sci (Lond) 131:87–103CrossRef Eklund L, Kangas J, Saharinen P (2017) Angiopoietin-Tie signalling in the cardiovascular and lymphatic systems. Clin Sci (Lond) 131:87–103CrossRef
50.
Zurück zum Zitat Chong HC, Tan CK, Huang RL, Tan NS (2012) Matricellular proteins: a sticky affair with cancers. J Oncol 2012:351089CrossRef Chong HC, Tan CK, Huang RL, Tan NS (2012) Matricellular proteins: a sticky affair with cancers. J Oncol 2012:351089CrossRef
51.
Zurück zum Zitat Rogers NM, Sharifi-Sanjani M, Yao M, Ghimire K, Bienes-Martinez R, Mutchler SM, Knupp HE, Baust J, Novelli EM, Ross M, St. Croix C, Kutten JC, Czajka CA, Sembrat JC, Rojas M, Labrousse-Arias D, Bachman TN, Vanderpool RR, Zuckerbraun BS, Champion HC, Mora AL, Straub AC, Bilonick RA, Calzada MJ, Isenberg JS (2017) TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction. Cardiovasc Res 113:15–29CrossRef Rogers NM, Sharifi-Sanjani M, Yao M, Ghimire K, Bienes-Martinez R, Mutchler SM, Knupp HE, Baust J, Novelli EM, Ross M, St. Croix C, Kutten JC, Czajka CA, Sembrat JC, Rojas M, Labrousse-Arias D, Bachman TN, Vanderpool RR, Zuckerbraun BS, Champion HC, Mora AL, Straub AC, Bilonick RA, Calzada MJ, Isenberg JS (2017) TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction. Cardiovasc Res 113:15–29CrossRef
Metadaten
Titel
Profile of fibrosis-related gene transcripts and megakaryocytic changes in the bone marrow of myelodysplastic syndromes with fibrosis
verfasst von
Kais Hussein
Angelika Stucki-Koch
Hans Kreipe
Publikationsdatum
30.06.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 11/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3411-9

Weitere Artikel der Ausgabe 11/2018

Annals of Hematology 11/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.