Macrophages and dendritic cells (DCs) are crucial for immune and inflammatory responses and belong to a network of cells that has been termed the mononuclear phagocyte system (MPS). However, the origin and lineage of these cells remain poorly understood. Here, we describe the isolation and clonal analysis of a mouse bone marrow progenitor that is specific for monocytes, several macrophage subsets, and resident spleen DCs in vivo. It was also possible to recapitulate this differentiation in vitro by using treatment with the cytokines macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Thus, macrophages and DCs appear to renew from a common progenitor, providing a cellular and molecular basis for the concept of the MPS.

Melanoma represents approximately 4% of human skin cancers, yet accounts for approximately 80% of deaths from cutaneous neoplasms (1). Although progress has been made in understanding the genetics of the molecular events underlying melanoma oncogenesis (2-4), the clinical challenge remains enormous. A genetic hallmark of melanoma is the presence of activating mutations in the oncogenes BRAF and NRAS, which are present in 70% and 15% of melanomas, respectively, and lead to constitutive activation of mitogen-activated protein kinase pathway signaling (3,5). However, molecules that inhibit mitogen-activated protein kinase pathway-associated kinases, like BRAF and MEK, have shown only limited efficacy in the treatment of metastatic melanoma (6). Thus, a deeper understanding of the cross talk between signaling networks and the complexity of melanoma progression should lead to more effective therapy.Hedgehog (HH) signaling is controlled at the cell surface by two transmembrane proteins, the tumor suppressor Patched-1 (PTCH1), which acts as a HH receptor, and the oncoprotein Smoothened (SMO). In the absence of HH, PTCH1 maintains SMO in an inactive state. In the presence of any of the three HH ligands (Sonic, Indian, or Desert HH), inhibition of SMO by PTCH1 is alleviated and a signal is transduced that leads to the nuclear translocation and activation of GLI family transcription factors (7,8). GLIs are often overexpressed in cancers and contribute to the progression of a variety of neoplasms via regulation of cell cycle progression and apoptosis (9,10). One recent study (11) Article

To evaluate the ability of high-resolution ultrasonography (hrUS) to detect sentinel-node (SN) melanoma metastases preoperatively before sentinel-node biopsy (SNB), to define hrUS resolution, and to evaluate which US criteria should be used. During a 6.5-year period, 131 consecutive patients with 132 >or=1-mm thick or ulcerated cutaneous melanomas, who were followed up at a single center, were enrolled. All patients underwent preoperative regional lymph-node hrUS and SNB. We used the recently evaluated ultrasonographic stringent and nonstringent hrUS criteria to detect SN metastases. Sizes of the SN metastatic deposits were measured under light microscopy. Thirty-five (27%) patients had a positive SNB. HrUS identified only three positive SNs as being metastatic. Sensitivity and specificity using stringent criteria were 8.8% [95% confidence interval (CI, 2.3-24.8%) and 95.9% (95% CI, 89.3-98.7%)], respectively. Positive-predictive value was 42.9% (95% CI, 11.9-79.9%). The nonstringent criteria provided four additional true-positive results, but lowered specificity (89.8%; 95% CI, 81.6-94.7%) with no significant improvement in sensitivity (20.6%; 95% CI, 9.3-38.4%). Positive-predictive value using nonstringent criteria was 41.2% (95% CI, 19.3-66.4%). HrUS failed to detect all metastatic deposits <5 mm in diameter. HrUS assessment of early-stage melanomas cannot replace surgical SNB. Owing to its low positive-predictive value, hrUS was unable to identify patients who would have to proceed directly to completion lymphadenectomy.

Adult T-cell leukemia/lymphoma (ATLL), a T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1), develops in the majority of cases in individuals who were infected with HTLV-1 as young children, by their mother during prolonged breastfeeding. We report the case of a Caucasian French man, whose parents were HTLV-1-seronegative and who developed ATLL after HTLV-1 sexual transmission by a Cameroonian woman. This hypothesis was corroborated by genotyping of the patient's virus, which revealed an HTLV-1B strain, found only in Central Africa, especially in Cameroon. Thus, ATLL may develop after HTLV-1 infection during adulthood, outside breastfeeding.

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Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell lymphoproliferation caused by human T-cell lymphotropic virus type-1 (HTLV-1). This oncogenic human retrovirus can be acquired by mother-to-child transmission through prolonged breast-feeding, sexual transmission, or from transfused infected blood cells or intravenous drug abuse. HTLV-1 infects approximately 5-10 million individuals worldwide and, among them, 1-5% will develop ATLL during their lifetime. Four major geographic molecular subtypes (genotypes) have been reported including the cosmopolitan a-subtype, the Central African b-subtype, the Central African/Pygmies d-subtype and the Australo-Melanesian c-subtype. The results of several studies showed that most cases of ATLL develop in individuals who have been infected with HTLV-1 as young children via their mothers' breast milk. The very rare ATLL cases observed following transfusion or sexual transmission are still being debated. Here, we report on a Caucasian French patient, with HTLV-1-seronegative parents, who developed ATLL, characterized by a clonal T cell skin proliferation of CD4+ and CD25+ cells, 18 years after highly probable sexual transmission of HTLV-1 through repeated unprotected sexual intercourse with a Cameroonian woman. Indeed, genotyping of the patient's virus revealed infection with an HTLV-1 b-subtype strain, typically of Central African origin, especially Cameroon. This case definitively confirms the hypothesis that ATLL can develop, albeit rarely, after infection during adulthood, outside breastfeeding.