eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
vol. 69
Original paper

Increased angiogenesis seems to correlate with inferior overall survival in myeloid sarcoma patients

Pier P. Piccaluga, Stefania Paolini, Mohsen Navari, Maryam Etebari, Giuseppe Visani, Stefano Ascani

Pol J Pathol 2018; 69 (3): 254-265
Online publish date: 2018/11/20
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Myeloid sarcomas (MS) are tumors composed by myeloid elements and developing outside bone marrow. The prognosis is overall poor, only stem cell transplantation being consistently reposted as a potentially curative approach.

In this study we explored whether microvessel density, a biomarker of angiogenesis, might be relevant in MS. We studied 60 MS, 24 acute myeloid leukemia, 5 normal bone marrow samples and 2 cases of extramedullary hemopoiesis in patients without evidence of hematological malignancy. We used immunohistochemistry (anti-CD34) to identify and quantify micro-vessel density (MVD) and micro-vessel grading (MVG). We found that MS had significantly higher MVD and MVG than normal bone marrow (p = 0.0002 and p < 0.001, respectively). We then found that cases with monocytic morphology had significantly higher MVD than myelo-monocytic and blastic ones (p = 0.005), while no differences were recorded based on extramedullary site. Finally, we found that higher MVD and higher MVG were associated with inferior outcome in terms of overall survival in multivariate analysis (p = 0.05 and p = 0.02, respectively), when censoring for stem cell transplantation was undertaken.

In conclusion, we documented for the first time that increased angiogenesis is characteristic of MS and correlates with survival, suggesting that anti-angiogenic approaches might deserve a clinical evaluation in this setting.

myeloid sarcoma, angiogenesis, micro-vessel density, immunohistochemistry, anti-angiogenic therapy

Pileri S, Orazi A, Falini B. Myeloid sarcoma. In: Swerdlow S, Campo E, Harris NL, et al. (eds.) WHO Classification of tumors of hematopoietic and lymphoid tissues. V ed. IARC, Lyon 2017; 140-141.
Piccaluga PP, Ascani S, Agostinelli C, et al. Myeloid sarcoma of liver: an unusual cause of jaundice. Report of three cases and review of literature. Histopathology 2007; 50: 802-805.
Pileri SA, Ascani S, Cox MC, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007; 21: 340-350.
Falini B, Lenze D, Hasserjian R, et al. Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas. Leukemia 2007; 21: 1566-1570.
Quintanilla-Martinez L, Zukerberg LR, Ferry JA, et al. Extramedullary tumors of lymphoid or myeloid blasts. The role of immunohistology in diagnosis and classification. Am J Clin Pathol 1995; 104: 431-443.
Mirza MK, Sukhanova M, Stolzel F, et al. Genomic aberrations in myeloid sarcoma without blood or bone marrow involvement: characterization of formalin-fixed paraffin-embedded samples by chromosomal microarrays. Leuk Res 2014; 38: 1091-1096.
Li Z, Stolzel F, Onel K, et al. Next generation sequencing reveals clinically actionable molecular markers in myeloid sarcoma. Leukemia 2015; 29: 2113-2116.
Movassaghian M, Brunner AM, Blonquist TM, et al. Presentation and outcomes among patients with isolated myeloid sarcoma: a Surveillance, Epidemiology, and End Results database analysis. Leuk Lymphoma 2014; 56: 1698-1703.
Peker D, Parekh V, Paluri R, et al. Clinicopathological and molecular features of myeloid sarcoma as initial presentation of therapy-related myeloid neoplasms: a single institution experience. Int J Hematol 2014; 100: 457-463.
Gimbrone MA Jr., Leapman SB, Cotran RS, et al. Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 1972; 136: 261-276.
Folkman J, Watson K, Ingber D, et al. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 1989; 339: 58-61.
Cao Y, Arbiser J, D’Amato RJ, et al. Forty-year journey of angiogenesis translational research. Sci Transl Med 2011; 3: 114rv3.
Vacca A, Ribatti D, Roncali L, et al. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 1994; 87: 503-508.
Ribatti D, Vacca A, Nico B, et al. Angiogenesis spectrum in the stroma of B-cell non-Hodgkin’s lymphomas. An immunohistochemical and ultrastructural study. Eur J Haematol 1996; 56: 45-53.
Vacca A, Ribatti D, Presta M, et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood 1999; 93: 3064-3073.
Pruneri G, Bertolini F, Soligo D, et al. Angiogenesis in myelodysplastic syndromes. Br J Cancer 1999; 81: 1398-1401.
Mesa RA, Hanson CA, Rajkumar SV, et al. Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia. Blood 2000; 96: 3374-3380.
Piccaluga PP, Visani G, Pileri SA, et al. Clinical efficacy and antiangiogenic activity of thalidomide in myelofibrosis with myeloid metaplasia. A pilot study. Leukemia 2002; 16: 1609-1614.
Piccaluga PP, Visani G, Finelli C, et al. Efficacy of thalidomide in the treatment of myelodysplastic syndromes. Haematologica 2002; 87: ELT18.
Pruneri G, Ponzoni M, Ferreri AJ, et al. Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol 2002; 118: 817-820.
Pruneri G, Bertolini F, Baldini L, et al. Angiogenesis occurs in hairy cell leukaemia (HCL) and in NOD/SCID mice transplanted with the HCL line Bonna-12. Br J Haematol 2003; 120: 695-698.
Padro T, Ruiz S, Bieker R, et al. Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia. Blood 2000; 95: 2637-2644.
Pileri SA, Roncador G, Ceccarelli C, et al. Antigen retrieval techniques in immunohistochemistry: comparison of different methods. J Pathol 1997; 183: 116-123.
Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 1991; 324: 1-8.
Heimburg S, Oehler MK, Papadopoulos T, et al. Prognostic relevance of the endothelial marker CD 34 in ovarian cancer. Anticancer Res 1999; 19 (4A): 2527-2529.
Kaplan E, Meier P. Non-parametric estimation from incomplete observation. JAMA 1958; 58: 457-481
Cox D. Regression models and life-tables. J R Stat Soc 1982; 34: 187-220.
Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966; 50: 163-170.
Went P, Agostinelli C, Gallamini A, et al. Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol 2006; 24: 2472-2479.
Arber D, Peterson L, Brunning R, et al. Acute myeloid leukaemia, not otherwise specified. In: Swerdlow S, Campo E, Harris NL et al. (eds.). WHO Classification of tumors of hematopoietic and lymphoid tissues. IV ed. IARC, Lyon 2008; 130-139.
Byrd JC, Weiss RB. Recurrent granulocytic sarcoma. An unusual variation of acute myelogenous leukemia associated with 8;21 chromosomal translocation and blast expression of the neural cell adhesion molecule. Cancer 1994; 73: 2107-2112.
Raanani P, Shpilberg O, Ben-Bassat I. Extramedullary disease and targeted therapies for hematological malignancies – is the association real? Ann Oncol 2007; 18: 7-12.
Dias S, Hattori K, Heissig B, et al. Inhibition of both paracrine and autocrine VEGF/ VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias. Proc Natl Acad Sci U S A 2001; 98: 10857-10862.
Dias S, Shmelkov SV, Lam G, Rafii S. VEGF(165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition. Blood 2002; 99: 2532-2540.
Ghannadan M, Wimazal F, Simonitsch I, et al. Immunohistochemical detection of VEGF in the bone marrow of patients with acute myeloid leukemia. Correlation between VEGF expression and the FAB category. Am J Clin Pathol 2003; 119: 663-671.
Santos SC, Dias S. Internal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia through distinct signaling pathways. Blood 2004; 103: 3883-3889.
Barosi G, Grossi A, Comotti B, et al. Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 2001; 114: 78-83.
Canepa L, Ballerini F, Varaldo R, et al. Thalidomide in agnogenic and secondary myelofibrosis. Br J Haematol 2001; 115: 313-315.
Pozzato G, Zorat F, Nascimben F, et al. Thalidomide therapy in compensated and decompensated myelofibrosis with myeloid metaplasia. Haematologica 2001; 86: 772-773.
Steins MB, Padro T, Bieker R, et al. Efficacy and safety of thalidomide in patients with acute myeloid leukemia. Blood 2002; 99: 834-839.
Karp JE, Gojo I, Pili R, et al. Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-d-arabinofuranosylcytosine, mitoxantrone, and bevacizumab. Clin Cancer Res 2004; 10: 3577-3585.
List A, Kurtin S, Roe DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. New Eng J Med 2005; 352: 549-557.
Reichert F, Barak V, Tarshis M, et al. Anti-angiogenic effects and regression of localized murine AML produced by anti-VEGF and anti-Flk-1 antibodies. Eur J Haematol 2005; 75: 41-46.
Barr P, Fu P, Lazarus H, et al. Antiangiogenic activity of thalidomide in combination with fludarabine, carboplatin, and topotecan for high-risk acute myelogenous leukemia. Leuk Lymphoma 2007; 48: 1940-1949.
Lancet JE, List AF, Moscinski LC. Treatment of deletion 5q acute myeloid leukemia with lenalidomide. Leukemia 2007; 21: 586-588.
Raza A, Mehdi M, Mumtaz M, et al. Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Cancer 2008; 113: 1596-1604.
Fehniger TA, Byrd JC, Marcucci G, et al. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood 2009; 113: 1002-1005.
Quintas-Cardama A, Kantarjian HM, et al. Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis. J Clin Oncol 2009; 27: 4760-4766.
Tefferi A, Verstovsek S, Barosi G, et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol 2009; 27: 4563-4569.
Mesa RA, Pardanani AD, Hussein K, et al. Phase1/-2 study of Pomalidomide in myelofibrosis. Am J Hematol 2010; 85: 129-130.
Visani G, Ferrara F, Di Raimondo F, et al. Low-dose lenalidomide plus cytarabine induce complete remission that can be predicted by genetic profiling in elderly acute myeloid leukemia patients. Leukemia 2014; 28: 967-970.
Meyer SC, Levine RL. Translational implications of somatic genomics in acute myeloid leukaemia. Lancet 2014; 15: e382-394.
Walter RB, Othus M, Paietta EM, et al. Effect of genetic profiling on prediction of therapeutic resistance and survival in adult acute myeloid leukemia. Leukemia 2015; 29: 2104-2107.
Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010; 116: 354-365.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe