دورية أكاديمية
MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia.
| العنوان: | MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia. |
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| المؤلفون: | Rauch PJ; Hematology, University Hospital and University of Zurich, Zurich, Switzerland.; Department of Medicine, Boston University School of Medicine, Boston, MA., Ellegast JM; Hematology, University Hospital and University of Zurich, Zurich, Switzerland., Widmer CC; Hematology, University Hospital and University of Zurich, Zurich, Switzerland., Fritsch K; Hematology, University Hospital and University of Zurich, Zurich, Switzerland., Goede JS; Hematology, University Hospital and University of Zurich, Zurich, Switzerland., Valk PJ; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands; and., Löwenberg B; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands; and., Takizawa H; Hematology, University Hospital and University of Zurich, Zurich, Switzerland.; International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan., Manz MG; Hematology, University Hospital and University of Zurich, Zurich, Switzerland. |
| المصدر: | Blood [Blood] 2016 Nov 03; Vol. 128 (18), pp. 2253-2257. Date of Electronic Publication: 2016 Aug 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Leukemia, Myeloid, Acute/*pathology , Neutropenia/*physiopathology , Receptors, Thrombopoietin/*biosynthesis , Thrombocytopenia/*physiopathology, Cohort Studies ; Gene Knock-In Techniques ; Hematopoiesis/physiology ; Heterografts ; Humans ; Leukemia, Myeloid, Acute/complications ; Leukemia, Myeloid, Acute/metabolism ; Neutropenia/etiology ; Thrombocytopenia/etiology ; Thrombopoietin/blood ; Transcriptome |
| مستخلص: | Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL hi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. (© 2016 by The American Society of Hematology.) |
| التعليقات: | Comment in: Blood. 2016 Nov 3;128(18):2195-2197. (PMID: 27811189) |
| المشرفين على المادة: | 0 (Receptors, Thrombopoietin) 143641-95-6 (MPL protein, human) 9014-42-0 (Thrombopoietin) |
| تواريخ الأحداث: | Date Created: 20160831 Date Completed: 20170728 Latest Revision: 20220311 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1182/blood-2016-04-711986 |
| PMID: | 27574191 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood-2016-04-711986 |