Overexpression of c-myb in leukaemic and non-leukaemic variants of cutaneous T-cell lymphoma.

BACKGROUND: The c-myb oncogene is a transcription factor that regulates proliferation, differentiation and apoptosis of haematopoietic cells and activated T cells by binding to promoter sequences of such genes as c-myc or bcl-2 that are expressed in cutaneous T-cell lymphoma (CTCL). OBJECTIVE: Our study was performed in order to evaluate c-myb expression as a quantitative parameter for differential diagnosis in leukaemic and non-leukaemic variants of CTCL. METHODS: c-myb expression was analysed in lesional skin and in the peripheral blood of 21 patients with mycosis fungoides (MF), 15 patients with Sézary syndrome (SS) and 15 patients with inflammatory skin diseases using immunohistochemistry and semiquantitative as well as quantitative RT-PCR. RESULTS: Immunohistochemistry confirmed expression of c-myb in the lesional skin of the majority of CTCL patients with a tendency towards higher expression in SS (1.86 +/- 0.5) versus MF (1.2 +/- 0.7) while c-myb was absent from the lesional skin of patients with inflammatory skin diseases. c-myb was overexpressed in the peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression level (51,335.31 +/- 31,960.32 AU in SS vs. 1,226.35 +/- 1,258.29 AU in MF using semiquantitative RT-PCR, and 5.72 x 10(-2) +/- 2.27 x 10(-2) in SS vs. 0.91 x 10(-2) +/- 1.18 x 10(-2) in MF vs. 0.24 x 10(-2) +/- 0.11 x 10(-2) in inflammatory skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of SS patients and cell lines in vitro showed the highest c-myb expression levels upon quantitative RT-PCR (23.27 x 10(-2) and 10.78 x 10(-2) +/- 7.24 x 10(-2)). CONCLUSION: Overexpression of c-myb in skin lesions of both non-leukaemic and leukaemic CTCL independent of the stage of the disease indicates that it acts early in disease development. Nevertheless, if positive, c-myb expression in lesional skin is a clear-cut diagnostic marker for CTCL as compared to inflammatory skin diseases. High-level expression of c-myb in the peripheral blood as assessed by quantitative RT-PCR constitutes an additional diagnostic parameter for SS and may be especially useful in cases in which morphological determination of Sézary cells or FACS analysis of CD7 and CD26 remain inconclusive.

Myelinated and unmyelinated fibers in sural nerve biopsy of a case with lepromatous leprosy--a quantitative approach.

A 64-year-old Cambodian male with lepromatous leprosy of several months' duration, with only brief previous treatment, had symmetrical patchy loss of pain and thermal sensibility including the lateral foot regions. Quantitative assessment by light and electron microscopy revealed normal counts of myelinated fibers (MF) and an increased number of unmyelinated fibers (UF). The respective abnormal histograms and the qualitative differentiation of UF-associated Schwann cells suggested a combination of segmental demyelination with Wallerian degeneration of MF, and a loss of genuine UF, concomitant with considerable regenerative activity of both fiber populations.

Cylindrical spirals in skeletal muscle: a further observation with clinical, morphological, and biochemical analysis.

Cylindrical spirals are abnormal uniform membranous inclusions in skeletal muscle, usually confined to type 2 fibers. Hitherto, only five cases have been published with various clinical syndromes. Here, a case is presented for the first time with detailed electrophysiological, histometrical, and biochemical analysis: a 60-year-old man with slowly progressing polyneuropathy confirmed by electrophysiological findings, and a history of diabetes, alcoholism, nicotine abuse, and weight reduction. In various muscle biopsies, large aggregates of cylindrical spirals were found almost exclusively in type 2B fibers. Obviously, the aggregates were derived from abnormal perinuclear and, therefore, mainly subsarcolemmal tubulovesicular structures. Morphometrical, histochemical, and biochemical analysis of muscle revealed no further information about the nature of these inclusions. They were not present in skin biopsy containing subcutaneous nerves.