Cytogenetic abnormalities in PHA‐stimulated lymphocytes from patients with Langerhans cell histiocytosis

Abstract

The aetiopathogenesis of Langerhans cell histiocytosis (LCH) is still undefined. Constitutional abnormalities in LCH have rarely been reported. One study showed chromosomal instability in lesional cells from three patients. No chromosomal studies are available on peripheral blood lymphocytes. Peripheral blood lymphocytes were analysed for the presence of chromatid and/or chromosomal breaks and structural rearrangements. A fluorescence in situ hybridization (FISH) painting technique was also applied in two cases. Sixteen patients with multisystem (MS, n = 11) or single system (SS, n = 5) LCH were studied, either at the diagnosis (n = 8), during treatment (n = 2) or during follow‐up, when asymptomatic (n = 6). Thirteen patients had chromosomal abnormalities. Eleven patients (69%) had chromatid and chromosomal breaks in 7–45% of cells. Overall, chromosome and chromatid breaks were significantly more frequent in the 11 patients with MS disease than in the five patients with SS disease: the mean percentage of cells showing chromosome and chromatid breaks was 13·4% in MS patients vs. 6·2% in SS patients (P = 0·003). Chromosomal abnormalities may be found in phytohaemagglutinin (PHA)‐stimulated peripheral blood lymphocytes of LCH patients at diagnosis, during the disease course and even during long‐term follow‐up, more frequently in MS disease. Chromosome instability may be considered as either a basic genetic instability or as a landmark of reaction to an environmental agent (viral?) that, through genome alteration, may play a role in histiocyte proliferation and, in some cases, also in the increased risk of malignancy.

Langerhans cell histiocytosis and human herpes virus 6 (HHV‐6), an analysis by real‐time polymerase chain reaction

“…18,24,40,51 -54 Additionally, some chromosomal instabilities have been described in lymphocytes of LCH patients, which may be a result of a viral insult. [54][55][56] Viruses such as HHV-6 are known to induce cytokine production by interfering with cellular function. Patients with LCH have been shown to abnormally produce at least 10 different cytokines, most of which are of T-cell origin, 45 and CD34þ hemopoietic precursor cells cultured in the presence of cytokines, including granulocyte-macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor a (TNFa), have been shown to take on the complete Langerhans cell phenotype.…”

Telomere length shortening in Langerhans cell histiocytosis

“…Characteristics supporting an immunologically mediated disorder secondary to an endogenous or exogenous inciting cause include the occurrence of occasional, spontaneous remissions, the failure to detect aneuploidy or karyotypic abnormalities and the inability to propagate LCH cells in vitro for more than a few days (Nezelof & Basset, 2004). Data supporting a primary neoplastic disorder include the demonstration that LCH represents a clonal proliferation of immature LC (Willman et al, 1994;Yu et al, 1994), the familial occurrence in some instances (Arico et al, 1999), microsatellite instability and several, characteristic genomic losses and gains (Betts et al, 1998;Scappaticci et al, 2000;Murakami et al, 2002).…”

Molecular Genetic Abnormalities in the Pathogenesis of Hematologic Malignancies and Corresponding Changes in Cell Signaling Systems

“…Часто сохраняется нормальный кариотип, хромосомные аномалии довольно редки [110][111][112][113][114].…”