Bone marrow involvement in cutaneous mastocytosis

Fearfield, L.; Francis, N.; Henry, Kristin; Costello, Collin M.; Bunker, C.B.

doi:10.1046/j.1365-2133.2001.04084.x

Cited by 19 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, increased mast cell numbers or mast cell dysplasia of the bone marrow have been demonstrated in 45–92% of patients with adult onset disease [10, 11]and in 18% of pediatric patients [12]. Similarly, c-kit mutations have so far been demonstrated in all adults with nonfamiliar CM studied, irrespective of bone marrow involvement, whereas these changes were not found by us in any of the childhood onset cases [13]and are reported only in rare pediatric patients with severe forms of the disease [reviewed in 3].…”

Section: Systemic Involvementmentioning

confidence: 99%

Cutaneous Mastocytosis – Clinical Heterogeneity

Hartmann

Henz

2002

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

Section: Systemic Involvementmentioning

confidence: 99%

Cutaneous Mastocytosis – Clinical Heterogeneity

Hartmann

Henz

2002

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…However, it should be noted that some cases of cutaneous mastocytosis have been reported that seemingly do not involve the bone marrow. 49 Regardless, our findings show that PTEN deficiency in MCs causes dysregulated proliferation with many of the features of systemic mastocytosis.…”

Section: Mc-specific Pten Deletion In Vivo Causes Enhanced Allergic Rmentioning

confidence: 86%

“…A similar enhanced proliferative environment has been described in the bone marrow of patients with systemic mastocytosis, where MCs are found to aggregate around lymphoid cells in a microenvironment that contains high levels of SCF. 5,49 A diagnostic feature of systemic mastocytosis is the increased numbers of MCs in the bone marrow, a characteristic we did not observe in PTEN-deficient mice. However, it should be noted that some cases of cutaneous mastocytosis have been reported that seemingly do not involve the bone marrow.…”

Section: Mc-specific Pten Deletion In Vivo Causes Enhanced Allergic Rmentioning

confidence: 99%

PTEN deficiency in mast cells causes a mastocytosis-like proliferative disease that heightens allergic responses and vascular permeability

Furumoto

Charles

Olivera

et al. 2011

Blood

View full text Add to dashboard Cite

Kit regulation of mast cell proliferation and differentiation has been intimately linked to the activation of phosphatidylinositol 3-OH kinase (PI3K). The activating D816V mutation of Kit, seen in the majority of mastocytosis patients, causes a robust activation of PI3K signals. However, whether increased PI3K signaling in mast cells is a key element for their in vivo hyperplasia remains unknown. Here we report that dysregulation of PI3K signaling in mice by deletion of the phosphatase and tensin homolog (Pten) gene (which regulates the levels of the PI3K product, phosphatidylinositol 3,4,5-trisphosphate) caused mast cell hyperplasia and increased numbers in various organs. Selective deletion of Pten in the mast cell compartment revealed that the hyperplasia was intrinsic to the mast cell. Enhanced STAT5 phosphorylation and increased expression of survival factors, such as Bcl-XL, were observed in PTENdeficient mast cells, and these were further enhanced by stem cell factor stimulation. Mice carrying PTEN-deficient mast cells also showed increased hypersensitivity as well as increased vascular permeability. Thus, Pten deletion in the mast cell compartment results in a mast cell proliferative phenotype in mice, demonstrating that dysregulation of PI3K signals is vital to the observed mast cell hyperplasia.(Blood. 2011;118(20): 5466-5475) IntroductionMast cells (MCs) are innate immune cells that also serve to amplify adaptive immunity. 1 They are best known for their role as effector cells in allergic disease, 2 but there is considerable evidence of a beneficial role for these cells in host defense and immune regulation. 3 In various pathologic circumstances, MC numbers can be increased because of hyperplasia or neoplastic transformation. 4,5 Mastocytosis is a term used to collectively describe MC hyperplasia/ neoplasia in one or more organs. Systemic mastocytosis normally involves one or more visceral organs with or without skin involvement. The majority of patients with mastocytosis carry a somatic mutation in the Kit proto-oncogene, the receptor for SCF that is central to MC proliferation and differentiation. Substitution of D for V at position 816 in the kinase domain of the receptor results in constitutive (SCF-independent) activation of Kit and enhanced MC proliferation. 6 It is well known that signals generated by SCF engagement of Kit are highly dependent on the activity of phosphatidylinositol 3-OH kinase (PI3K). [7][8][9][10] In addition, PI3K activity is also increased by the D816V mutation of Kit. 9 Proliferation of murine MCs is also partly dependent on IL-3 and its receptor (IL-3R). 11,12 Human intestinal MCs also express functional IL-3R, and IL-3 stimulation causes enhanced growth rates and effector responses. 13 Interestingly, IL-3R activity and its role in regulating proliferative responses are also tightly coupled to the activation of PI3K. 14 In addition, STAT5 is also important to the transcriptional activity induced by the IL-3R and c-Kit, and STAT5-PI3K-Akt signals are known to be essenti...

show abstract

“…A betegség minden élet-korban jelentkezhet, irodalmi adatok szerint az esetek mintegy 15%-ában egészen születéstől kezdve fennáll, 30%-ban hat hónapos korban, 10%-ban 15 éves kor kö-rül kerül felismerésre, és 35%-ban felnőttkorban manifesztálódik [2]. A felnőttkori megjelenés hozzávetőleg 45-92%-ban már csontvelő-érintettséggel jár [2,3,4]. Általánosságban elmondható, hogy csupán bőrérintett-ség esetén a betegség jó prognózisú.…”

Section: Megbeszélésunclassified

“…További megfi gyelések szerint a maculopapulosus típus közel 50%-ában van csontvelő-érintettség, és a bőrben kimutatható a c-KIT-mutáció, függetlenül a csontvelő-érin-tettségtől [3,4,5,6,7].…”

Section: Hízósejt-sarcomaunclassified

Clinical observations in cutan mastocytosis

et al. 2013

View full text Add to dashboard Cite

Bevezetés: A mastocytosis a hízósejtek (mastocyták) felszaporodásával járó ritka megbetegedés, amely a WHO-besorolás szerint cutan és szisztémás formákra osztható. A klinikai tünetekhez a hízósejtek szöveti infi ltrációja és/vagy a mediátorfelszabadulás vezet. Célkitűzés: A szerzők a Semmelweis Egyetem Mastocytosis Hálózat részeként a jellegzetes bőrtüneteket mutató betegek kivizsgálásával szerzett tapasztalatainak összefoglalását tűzték ki célul. Módszer: Összesen 22 mastocytosisos felnőtt beteget vizsgáltak. A diagnózis felállítása bőrszövettani vizsgálat, csontvelővizs-gálat, D816V szomatikus c-KIT-mutációanalízis alapján történt. Eredmények: Húsz beteg esetében urticaria pigmentosát, egy esetben teleangiectasia macularis eruptiva perstanst észleltek. A bőr szövettani vizsgálata minden esetben igazolta a klinikai diagnózist. Cristabiopsziával 9/12 esetben a csontvelői részvétel alapján indolens szisztémás mastocytosis diagnózisa volt felállítható. c-KIT-mutációt (D816V) egy betegben igazoltak mind a csontvelőben, mind a bőrben. A betegek a klinikum függvényében antihisztamin, PUVA, a c-kit-szekvenálás eredménye alapján alfa-interferon vagy tirozinkináz-gátló terápiában részesültek. Következtetések: A mastocytosis diagnózisának felállításában a bőrgyógyász szerepe kiemelten fontos, de a betegség kiterjedtségének tisztázására a csontvelő vizsgálatát minden esetben tanácsos elvégezni. Orv. Hetil., 2013, 154, 1469-1475

show abstract

Bone marrow involvement in cutaneous mastocytosis

Abstract: Bone marrow involvement is common in adults with cutaneous mastocytosis.

Cited by 19 publications

References 27 publications

Cutaneous Mastocytosis – Clinical Heterogeneity

Cutaneous Mastocytosis – Clinical Heterogeneity

PTEN deficiency in mast cells causes a mastocytosis-like proliferative disease that heightens allergic responses and vascular permeability

Clinical observations in cutan mastocytosis

Contact Info

Product

Resources

About