China
Africa
Explore chapters and articles related to this topic
Pulmonary alveolar proteinosis
Published in Muhunthan Thillai, David R Moller, Keith C Meyer, Clinical Handbook of Interstitial Lung Disease, 2017
In some of the literature this has also been referred to as congenital PAP but hereditary or hPAP is becoming the preferred term because of the fairly wide range of gene defects (4) and timing of presentation that have been described. Better understanding of alveolar macrophage natural history and control suggest the possibility for radical treatment options, even ‘cure’ by pulmonary macrophage transplantation (5). In some cases there are clear inheritance patterns in a cohort of relatives while in others a more sporadic mutation may have occurred. The defect may be anywhere along the various surfactant control or alveolar macrophage control pathways culminating in the typical PAP phenotype. The easiest variants to understand are the mutations of CSF2RA or CSF2RB genes which encode GM-CSF receptor alpha or beta and subsequent macrophage failure typical of all forms of PAP. Some cases present in early infancy with a similar combination of physiology, imaging and histology to aPAP but with the added complication of afflicting small and immature children and babies with all that entails. In particular the WLL options in small children are much more complex when the child is too small for a typical double-lumen endobronchial tube used to safely separate left and right lungs during thoracic anaesthesia procedures.
The favorable prognostic value of the loss of sex chromosomes in patients with t(8;21) acute myeloid leukemia: an exploratory study
Published in Hematology, 2022
Lixia Zhu, Rongrong Chen, Xueying Li, Mixue Xie, Xiudi Yang, Jianai Sun, Mingyu Zhu, Xiaolong Zheng, Li Li, Jingjing Zhu, De Zhou, Wanzhuo Xie, Xiujin Ye
LOS is more frequently observed in t(8;21) AML than other subtypes of AML. There were several studies exploring the effect of LOS on the pathogenesis of t(8;21) AML. Kuchenbauer F et al found that AML1-ETO alone is not enough to induce tumorigenesis [19]. In their murine models, overexpression of AML1-ETO without additional genetic and molecular mutations did not show a leukemic transformation [20]. In another study, Matsuura et al discovered that the gene encoding the GM-CSF receptor α subunit (CSF2RA) on the human sex chromosome plays an unexpected tumor-suppressor role. The occurrence of LOS certainly accompanied by the loss of the tumor suppressive effect of GM-CSF [8]. Therefore, loss of the CSF2RA may be a critical mutation explaining the high incidence of LOS in t(8;21)(q22;q22). The studies above both explained the synergistic effect of LOS and AML1-ETO on pathogenesis of AML.
Advances in the genetics of acute lymphoblastic leukemia in adults and the potential clinical implications
Published in Expert Review of Hematology, 2018
Netanel A. Horowitz, Doaa Akasha, Jacob M. Rowe
Approximately 50% of patients with Ph-like ALL have overexpression of cytokine receptor-like factor 2 (CRLF2) [24]. CRFL2 pairs with interleukin-7 receptor α to form a heterodimeric thymic stromal lymphopoietin receptor implicated in early B cell development [26]. This gene is located on the pseudo-autosomal region 1(PAR1) of chromosomes Xp22/Yp11 [27]. The most common genetic alterations involving the CRFL2 gene are deletion of PAR1 which joins CRFL2 to P2RY8 gene resulting in a new CRFL2-P2RY8 transcript [28], and a translocation which joins CRFL2 to the immunoglobulin heavy chain gene IGH located on chromosome 14q32 [29]. Fusion of CLFR2 to another PAR1 gene, CSF2RA has also been described [30]. Among ALL patients harboring CFLR2 alterations, almost half have concomitant activating JAK1 or JAK2 mutations [31]. CRFL2 overexpression and JAK2 mutations collaborate and lead to constitutive activation of the JAK-STAT signalling [31]. Genetic abnormalities in the JAK2 protein without concomitant CFLR2 aberrations have been described in young adults with the Ph-like phenotype [32]. The JAK-STAT signaling pathway may also be activated by rearrangement of the erythropoietin receptor (EPOR-R) gene with other genes (IGH, IGK LAIR1 and THAD) which results in overexpression of EPOR-R that have lost negative regulatory domains. These cases have been demonstrated in about 1% of ALL patients [32].
Chronic interstitial lung diseases in children: diagnosis approaches
Published in Expert Review of Respiratory Medicine, 2018
Nadia Nathan, Laura Berdah, Keren Borensztajn, Annick Clement
Very rare cases of pediatric PAP have been associated with GM-CSF receptor defects [95,96]. The clinical presentation is heterogeneous, with patients being diagnosed in adulthood. The effects of GM-CSF are mediated through heterodimeric cell surface receptors that are expressed on a number of cell surfaces including macrophages, neutrophils and type 2 AEC. The GM-CSF receptors are composed of α chains encoded by the CSF2RA gene and β chains encoded by the CSF2RB gene. It is suggested that the GM-CSF receptor defect could be responsible for a lack of efficiency of the alveolar macrophages in recycling the SP, that accumulate in the alveolar space.