Infantile Myelofibrosis and Myeloproliferation with CDC42 Dysfunction
| Autor: | Alan B. Cantor, Inga Hofmann, Vijay G. Sankaran, David A. Williams, Dilnar Mahmut, Mitsutoshi Nakamura, Amy E. Geddis, Nour J. Abdulhay, Susan M. Parkhurst, Jeffrey M. Verboon, Becky Manes, Haydar Frangoul, Stacey Gabriel, Ah Ram Kim, Genevieve M. Crane, Daryl E. Klein, Thomas E. Akie, Namrata Gupta, Meghan E. Kapp, Satish K. Nandakumar |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology Germline mosaicism Disease GTPase CDC42 Biology 03 medical and health sciences 0302 clinical medicine Myeloproliferation Rho GTPases Exome Sequencing medicine Immunology and Allergy Humans Progenitor cell Myelofibrosis cdc42 GTP-Binding Protein bone marrow microenvironment Siblings Cell Cycle Infant Newborn Infant medicine.disease Hematopoiesis Haematopoiesis 030104 developmental biology HEK293 Cells Cellular Microenvironment Primary Myelofibrosis Mutation Cancer research Original Article 030217 neurology & neurosurgery |
| Zdroj: | Journal of Clinical Immunology |
| ISSN: | 1573-2592 0271-9142 2241-7990 |
| Popis: | Studies of genetic blood disorders have advanced our understanding of the intrinsic regulation of hematopoiesis. However, such genetic studies have only yielded limited insights into how interactions between hematopoietic cells and their microenvironment are regulated. Here, we describe two affected siblings with infantile myelofibrosis and myeloproliferation that share a common de novo mutation in the Rho GTPase CDC42 (Chr1:22417990:C>T, p.R186C) due to paternal germline mosaicism. Functional studies using human cells and flies demonstrate that this CDC42 mutant has altered activity and thereby disrupts interactions between hematopoietic progenitors and key tissue microenvironmental factors. These findings suggest that further investigation of this and other related disorders may provide insights into how hematopoietic cell-microenvironment interactions play a role in human health and can be disrupted in disease. In addition, we suggest that deregulation of CDC42 may underlie more common blood disorders, such as primary myelofibrosis. |
| Databáze: | OpenAIRE |
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