Mixed Myelodysplastic Syndrome and Myeloproliferative Disorder with Bone Marrow and Pulmonary Fibrosis: The Role of Megakaryocytes

Abstract

The case of an 80-year-old woman displaying myelodysplastic syndrome evolving into a myeloproliferative disorder with myelofibrosis and pulmonary fibrosis, is reported. This case is characterized by an initial presentation of a myelodysplastic syndrome with normal karyotype and moderate fibrosis, its evolution towards a myeloproliferative disorder with myelofibrosis and the worsening of pulmonary fibrosis in parallel to the acceleration of the myeloproliferative disorder and myelofibrosis. These features and the high concentration of plasma platelet factor-4 suggest a role of megakaryocyte/platelet degranulation in the development of fibrosis.

Megakaryocytes participate in the occurrence of bleomycin-induced pulmonary fibrosis

“…It has previously been demonstrated that the pathogenesis of chronic myelogenous leukemia, myeloproliferative disorder and scleroderma with pulmonary fibrosis complications may be associated with megakaryocyte infiltration in the lung [11][12][13][14]18 . Our studies demonstrate that the number of CD41 + megakaryocytes increased in the lung tissue after BLM challenge, which is consistent with previously studies, suggesting that megakaryocytes may be associated with the occurrence of lung fibrosis.…”

“…Multifaceted evidence suggests that megakaryocyte residents in the bone marrow contribute to idiopathic myelofibrosis [6][7][8][9][10] . Reports demonstrated that megakaryocyte infiltration in cases of chronic myelogenous leukemia 11,12 and myeloproliferative disorder 13,14 is associated with the occurrence of pulmonary fibrosis. In addition, many studies have shown that megakaryocytes in the lungs are closely related to several respiratory diseases, including diffuse alveolar damage, burns-induced lung injury, and pulmonary fibrosis in scleroderma [15][16][17][18] .…”

IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis

“…54 A similar process could be evoked in MMM, in which PF4 is highly increased in the BM microenvironment. 55,56 Interestingly, intramedullary accumulation of PF4 is suggested to promote the displacement of hematopoiesis to other organs such as liver and spleen. 54 Such a hypothesis is of pathophysiologic relevance with regard to MMM, in which medullary aplasia is associated with myeloid metaplasia in spleen and liver.…”

Platelets in Pulmonary Vascular Physiology and Pathology

“…In many cases, it is a reactive thrombocytosis secondary to lung inflammation developing during the natural history of PH. [85,86] But pulmonary hypertension also occurs in patients with post-splenectomy thrombocytosis [87] and myeloproliferative disease-associated thrombocytosis, [88] and it commonly develops in myelofibrosis with myeloid metaplasia. [82] How do these clinical conditions, each of which imposes unique changes on several elements within Virchow's triad, lead to pulmonary hypertension?…”