Current views in HTLV-I-associated adult T-cell leukemia/lymphoma

Abstract

Epidemiological studies have demonstrated that the relative percentage of malignant lymphoid proliferations varies widely according to geographical location and ethnic populations. HTLV-I is the etiological agent of adult T-cell leukemia/lymphoma (ATLL) and is also associated with cutaneous T-cell lymphoma (CTCL). However, a definite role of HTLV-I in mycosis fungoides (MF) and/or Sezary syndrome (SS) remains controversial. While most HTLV-I-infected individuals remain asymptomatic carriers, 1-5% will develop ATLL, an invariably fatal expansion of virus-infected CD4 + T cells. This low incidence and the long latency period preceding occurrence of the disease suggest that additional factors are involved in development of ATLL. In this review, diagnosis, clinical features, and molecular pathogenesis of HTLV-I are discussed. Am.

FOXP3, a selective marker for a subset of adult T-cell leukaemia/lymphoma

“…HTLV-1 provirus integration was confirmed in all ATLL samples by ELISA and Southern-blot techniques. 18,19 For comparison, we studied a large series of samples representing T-and B-cell neoplasms, including T-cell lymphoblastic lymphoma (four), peripheral T-cell lymphoma (20), angioimmunoblastic T-cell lymphoma (five), T-cell/natural killer cell lymphoma (five), anaplastic large cell lymphoma (nine), mycosis fungoides (15), B-cell lymphocytic leukaemia/lymphoma (14), mantle cell lymphoma (14), marginal zone B-cell lymphoma (12), diffuse large B-cell lymphoma (17), follicular lymphoma (17) and Burkitt's lymphoma (15). Informed consent was obtained from all patients included in the study under the supervision of the local ethical committees.…”

“…However, ATLL patients can present different clinical features resulting in a division of the disease into four clinical subtypes: acute (leukemic ATLL with a median survival of 6 months), lymphoma type ATLL (characterized by lymphadenopathy with a median survival of 10 months), chronic ATLL and smouldering ATLL (median survival of more than 24 months). 15 Progression from the indolent to acute variants occurs in 25% of cases.…”

The HTLV-I p30 Interferes with TLR4 Signaling and Modulates the Release of Pro- and Anti-inflammatory Cytokines from Human Macrophages

“…HTLV-I-infected monocytes produce dysfunctional dendritic cells because of improper differentiation, which do not stimulate autologous T-cells (12). HTLV-I-infected ATL patients have pronounced immunodeficiency associated with frequent opportunistic infections by various pathogens, including Pneumocystis carinii, Toxoplasma gondii, Cryptococcus neoformans, Candida albicans, Mycobacterium avium, and Aspergillus, Cytomegalovirus, and Strongyloides (13,14). HTLV-I regulatory protein p30 has been shown to suppress virus expression at both transcriptional and post-transcriptional levels.…”

Endocrine and metabolic disorders in HTLV-1 infected patients

“…[16][17] In 70%-80% of the acute ATLL form, the patients develop the humoral hypercalcemia of malignancy (HHM), a paraneoplastic syndrome characterized by hypercalcemia, osteoporosis and osteolytic lesions. [13][14][15]18,19 This suggests that there should be released or expressed molecules in ATLL cells performing a crucial role in HHM etiology. 20 The HHM of patients with acute ATLL is caused by mechanisms that act synergistically, affecting directly or indirectly the osteoclastic differentiation.…”

“…[13][14][15] It affects 5% of the patients, starting in the average age of 58 years-old. [16][17] In 70%-80% of the acute ATLL form, the patients develop the humoral hypercalcemia of malignancy (HHM), a paraneoplastic syndrome characterized by hypercalcemia, osteoporosis and osteolytic lesions.…”