Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
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Κυριακή 5 Μαρτίου 2017

The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome.

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The presence of CXCR4(+) CD1a(+) cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome.

Oncoimmunology. 2016 Mar;5(3):e1084463

Authors: Quispel WT, Stegehuis-Kamp JA, Blijleven L, Santos SJ, Lourda M, van den Bos C, van Halteren AG, Egeler RM

Abstract
PURPOSE: Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder characterized by tissue accumulating CD1a(+) histiocytes which frequently carry somatic mutations. Irrespective of mutation status, these LCH-cells display constitutively active kinases belonging to the MAPK pathway. We evaluated, in retrospect, the contribution of individual components of the MAPK-activating and chemotaxis-promoting TNF-CXCR4-CXCL12 axis to LCH manifestation and outcome.
EXPERIMENTAL DESIGN: CXCR4, CXCL12 and TNF protein expression was immunohistochemically analyzed in 70 LCH-affected biopsies. The presence of CXCR4(+)CD1a(+) cells in peripheral blood (PB) and/or bone marrow (BM) samples was evaluated by flowcytometry in 13 therapy-naive LCH-patients.
RESULTS: CXCL12 was detected in 68/70 (97%) biopsies. CXCR4(+)LCH-cells were present in 50/70 (71%) biopsies; their presence was associated with higher levels of intralesional TNF. Circulating CD1a(+)CXCR4(+) cells were detected in 4/13 (31%) therapy-naïve LCH-patients which displayed BRAF(V600E) (2/4), MAP2K1 (1/4) or no (1/4) mutations in their tissues. These CD11c co-expressing CD1a(+)CXCR4(+)cells migrated to CXCL12 in chemotaxis assays. Lesional CXCR4(+)LCH-cells were detected in 18/20 cases who presented with LCH manifestation at multiple sites and in 5/23 (22%) patients who developed additional lesions after initially presenting with a single lesion. The CXCR4 status at onset proved to be an independent risk factor for LCH reactivation in multivariate analysis (odds ratio 10.4, p = 0.034).
CONCLUSIONS: This study provides the first evidence that CXCR4 is involved in the homing and retention of LCH-cells in CXCL12-expressing tissues and qualifies CXCR4 as a candidate prognostic marker for less favorable disease outcome.

PMID: 28255525 [PubMed]



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