Altered Immunophenotypic Features of Peripheral Blood Platelets in Myelodysplastic Syndromes

Overview

Journal Haematologica

Specialty Hematology

Date 2012 Jan 25

PMID 22271903

Citations 15

Authors

Alex F Sandes

Mihoko Yamamoto

Sergio Matarraz

Maria de Lourdes L F Chauffaille

Sandra Quijano

Antonio Lopez

Tsutomu Oguro

Eliza Y S Kimura

Alberto Orfao

Affiliations

Soon will be listed here.

Abstract

Background: Multiparameter flow cytometric analysis of bone marrow and peripheral blood cells has proven to be of help in the diagnostic workup of myelodysplastic syndromes. However, the usefulness of flow cytometry for the detection of megakaryocytic and platelet dysplasia has not yet been investigated. The aim of this pilot study was to evaluate by flow cytometry the diagnostic and prognostic value of platelet dysplasia in myelodysplastic syndromes.

Design And Methods: We investigated the pattern of expression of distinct surface glycoproteins on peripheral blood platelets from a series of 44 myelodysplastic syndrome patients, 20 healthy subjects and 19 patients with platelet alterations associated to disease conditions other than myelodysplastic syndromes. Quantitative expression of CD31, CD34, CD36, CD41a, CD41b, CD42a, CD42b and CD61 glycoproteins together with the PAC-1, CD62-P, fibrinogen and CD63 platelet activation-associated markers and platelet light scatter properties were systematically evaluated.

Results: Overall, flow cytometry identified multiple immunophenotypic abnormalities on platelets of myelodysplastic syndrome patients, including altered light scatter characteristics, over-and under expression of specific platelet glycoproteins and asynchronous expression of CD34; decreased expression of CD36 (n = 5), CD42a (n = 1) and CD61 (n = 2), together with reactivity for CD34 (n = 1) were only observed among myelodysplastic syndrome cases, while other alterations were also found in other platelet disorders. Based on the overall platelet alterations detected for each patient, an immunophenotypic score was built which identified a subgroup of myelodysplastic syndrome patients with a high rate of moderate to severe alterations (score>1.5; n = 16) who more frequently showed thrombocytopenia, megakaryocytic dysplasia and high-risk disease, together with a shorter overall survival.

Conclusions: Our results show the presence of altered phenotypes by flow cytometry on platelets from around half of the myelodysplastic syndrome patients studied. If confirmed in larger series of patients, these findings may help refine the diagnostic and prognostic assessment of this group of disorders.

Citing Articles

Immunophenotyping myelodysplastic neoplasms: the role of flow cytometry in the molecular classification era.

Verigou E, Chatzilygeroudi T, Lazaris V, de Lastic A, Symeonidis A Front Oncol. 2024; 14:1447001.

PMID: 39544295 PMC: 11560873. DOI: 10.3389/fonc.2024.1447001.

Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in myelodysplastic neoplasms (MPO-MDS-Valid): protocol for a multicentre diagnostic accuracy study.

Planta C, Bret C, Manzoni D, Lhoumeau A, Mayeur Rousse C, Ticchioni M BMJ Open. 2024; 14(6):e081200.

PMID: 38889946 PMC: 11191800. DOI: 10.1136/bmjopen-2023-081200.

Clinical and Molecular Characteristics of Megakaryocytes in Myelodysplastic Syndrome.

Luo F, Zhao J, Chen Y, Peng Z, An R, Lu Y Glob Med Genet. 2024; 11(2):187-195.

PMID: 38860162 PMC: 11164576. DOI: 10.1055/s-0044-1787752.

Abnormal platelet immunophenotypes and percentage of giant platelets in myelodysplastic syndrome: A pilot study.

Wu Y, Gu M, Liu C, Huang W, Chu S, Wang T PLoS One. 2022; 17(11):e0278040.

PMID: 36409726 PMC: 9678267. DOI: 10.1371/journal.pone.0278040.

Platelet Defects in Acute Myeloid Leukemia-Potential for Hemorrhagic Events.

Bumbea H, Vladareanu A, Dumitru I, Popov V, Ciufu C, Nicolescu A J Clin Med. 2022; 11(1).

PMID: 35011859 PMC: 8745388. DOI: 10.3390/jcm11010118.

References

Arroyo J, Fernandez M, Hernandez J, Orfao A, San Miguel J, Del Canizo M . Impact of immunophenotype on prognosis of patients with myelodysplastic syndromes. Its value in patients without karyotypic abnormalities. Hematol J. 2004; 5(3):227-33. DOI: 10.1038/sj.thj.6200370. View

Curtis B, Ali S, Glazier A, Ebert D, Aitman T, Aster R . Isoimmunization against CD36 (glycoprotein IV): description of four cases of neonatal isoimmune thrombocytopenia and brief review of the literature. Transfusion. 2002; 42(9):1173-9. DOI: 10.1046/j.1537-2995.2002.00176.x. View

Braun T, Carvalho G, Grosjean J, Ades L, Fabre C, Boehrer S . Differentiating megakaryocytes in myelodysplastic syndromes succumb to mitochondrial derangement without caspase activation. Apoptosis. 2007; 12(6):1101-8. DOI: 10.1007/s10495-006-0030-z. View

Wells D, Benesch M, Loken M, Vallejo C, Myerson D, Leisenring W . Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood. 2003; 102(1):394-403. DOI: 10.1182/blood-2002-09-2768. View

Tomer A . Human marrow megakaryocyte differentiation: multiparameter correlative analysis identifies von Willebrand factor as a sensitive and distinctive marker for early (2N and 4N) megakaryocytes. Blood. 2004; 104(9):2722-7. DOI: 10.1182/blood-2004-02-0769. View

Houwerzijl E, Blom N, van der Want J, Vellenga E, de Wolf J . Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death. Leukemia. 2006; 20(11):1937-42. DOI: 10.1038/sj.leu.2404385. View

Levine R, Hazzard K, Lamberg J . The significance of megakaryocyte size. Blood. 1982; 60(5):1122-31. View

Tomer A, Harker L, BURSTEIN S . Flow cytometric analysis of normal human megakaryocytes. Blood. 1988; 71(5):1244-52. View

Ogata K, Kishikawa Y, Satoh C, Tamura H, Dan K, Hayashi A . Diagnostic application of flow cytometric characteristics of CD34+ cells in low-grade myelodysplastic syndromes. Blood. 2006; 108(3):1037-44. DOI: 10.1182/blood-2005-12-4916. View

10.

Verburgh E, Achten R, Louw V, Brusselmans C, Delforge M, Boogaerts M . A new disease categorization of low-grade myelodysplastic syndromes based on the expression of cytopenia and dysplasia in one versus more than one lineage improves on the WHO classification. Leukemia. 2007; 21(4):668-77. DOI: 10.1038/sj.leu.2404564. View

11.

Lorand-Metze I, Ribeiro E, Lima C, Batista L, Metze K . Detection of hematopoietic maturation abnormalities by flow cytometry in myelodysplastic syndromes and its utility for the differential diagnosis with non-clonal disorders. Leuk Res. 2006; 31(2):147-55. DOI: 10.1016/j.leukres.2006.04.010. View

12.

Yamamoto N, Akamatsu N, Sakuraba H, Yamazaki H, Tanoue K . Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type I) or the presence (type II) of glycoprotein IV on monocytes. Blood. 1994; 83(2):392-7. View

13.

Della Porta M, Malcovati L, Invernizzi R, Travaglino E, Pascutto C, Maffioli M . Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome. Leukemia. 2006; 20(4):549-55. DOI: 10.1038/sj.leu.2404142. View

14.

Lorand-Metze I, Califani S, Ribeiro E, Lima C, Metze K . The prognostic value of maturation-associated phenotypic abnormalities in myelodysplastic syndromes. Leuk Res. 2007; 32(2):211-3. DOI: 10.1016/j.leukres.2007.06.014. View

15.

Giannini S, Mezzasoma A, Guglielmini G, Rossi R, Falcinelli E, Gresele P . A new case of acquired Glanzmann's thrombasthenia: diagnostic value of flow cytometry. Cytometry B Clin Cytom. 2008; 74(3):194-9. DOI: 10.1002/cyto.b.20396. View

16.

Cutler J, Wells D, van de Loosdrecht A, de Baca M, Kalnoski M, Zehentner B . Phenotypic abnormalities strongly reflect genotype in patients with unexplained cytopenias. Cytometry B Clin Cytom. 2011; 80(3):150-7. DOI: 10.1002/cyto.b.20582. View

17.

Aziz K . An acquired form of Bernard Soulier syndrome associated with acute myeloid leukemia. Saudi Med J. 2005; 26(7):1095-8. View

18.

Stachurski D, Smith B, Pozdnyakova O, Andersen M, Xiao Z, Raza A . Flow cytometric analysis of myelomonocytic cells by a pattern recognition approach is sensitive and specific in diagnosing myelodysplastic syndrome and related marrow diseases: emphasis on a global evaluation and recognition of diagnostic pitfalls. Leuk Res. 2007; 32(2):215-24. DOI: 10.1016/j.leukres.2007.06.012. View

19.

van de Loosdrecht A, Westers T, Westra A, Drager A, van der Velden V, Ossenkoppele G . Identification of distinct prognostic subgroups in low- and intermediate-1-risk myelodysplastic syndromes by flow cytometry. Blood. 2007; 111(3):1067-77. DOI: 10.1182/blood-2007-07-098764. View

20.

Lopez-Holgado N, Arroyo J, Pata C, Villaron E, Sanchez Guijo F, Martin A . Analysis of hematopoietic progenitor cells in patients with myelodysplastic syndromes according to their cytogenetic abnormalities. Leuk Res. 2004; 28(11):1181-7. DOI: 10.1016/j.leukres.2004.02.007. View