The bone marrow stroma in hematological neoplasms—a guilty bystander
In the setting of hematological neoplasms, changes in the bone marrow (BM) stroma might arise from pressure exerted by the neoplastic clone in shaping a supportive microenvironment, or from chronic perturbation of the BM homeostasis. Under such conditions, alterations in the composition of the BM stroma can be profound, and could emerge as relevant prognostic factors. In this Review, we delineate the multifaceted contribution of the BM stroma to the pathobiology of several hematological neoplasms, and discuss the impact of stromal modifications on the natural course of these diseases. Specifically, we highlight the involvement of BM stromal components in lymphoid and myeloid malignancies, a…
Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion.
Abstract In myeloid malignancies, the neoplastic clone outgrows normal hematopoietic cells toward BM failure. This event is also sustained by detrimental stromal changes, such as BM fibrosis and osteosclerosis, whose occurrence is harbinger of a dismal prognosis. We show that the matricellular protein SPARC contributes to the BM stromal response to myeloproliferation. The degree of SPARC expression in BM stromal elements, including CD146+ mesenchymal stromal cells, correlates with the degree of stromal changes, and the severity of BM failure characterizing the prototypical myeloproliferative neoplasm primary myelofibrosis. Using Sparc−/− mice and BM chimeras, we demonstrate that SPARC contr…
An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults
Abstract Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future…
Bone marrow fibrosis and diagnosis of essential thrombocythemia
However, there are serious issues to beraisedconcerningtheauthors’analysisoftheclinicaldata,thecriteriausedtodiagnoseET,andthequantificationoffibrosis.Altogethertheauthors compared a heterogenous patient database, which included311 patients evaluated for presenting features, 299 for response totherapy,361forcomplicationrates,97forprogressionoffibrosis,andfour for reversal of BM fibrosis, so no single cohort with consistentfeatures was described throughout the study of 361 patients. Forexample, for the analysis of progression of fibrosis, only 97 (12%) oftheoriginal809patientsenteredintheUK-PT1trial
European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis: Haematologica 2012;97(3):360-5 - Comment
Any study of myeloproliferative neoplasms (MPNs) that lacks adequate clinical input is doomed to cause diagnostic uncertainty and increased controversy. In the paper by Buhr et al. published in Haematologica,[1][1] the authors studied 102 cases of essential thrombocythemia (ET) and early primary