Aberrant signaling in T-cell acute lymphoblastic leukemia: biological and therapeutic implications

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-ß, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL.

Adult T-cell leukemia-lymphoma in a patient with HTLV-I/II associated myelopathy

Chronic myelopathy associated with T-lymphotropic virus type I (HAM) has been described as an endemic disease in several areas of the world, meanwhile there are few papers describing the association between HAM and adult T cell leukemia-lymphoma. We report the case of a man that, after four years of progressive spastic paraparesis and neurogenic bladder, developed a clinical picture of a lymphoproliferative disorder characterized by dermal and systemic envolviment, mimicking mycosis fungoides/Sézary syndrome.

Histopathologic spectrum of AIDS-associated lesions in Maharaj Nakorn Chiang Mai Hospital.

The histopathological alterations in various organs and the presence of AIDS-associated lesions were studied in 86 biopsy and 29 necropsy specimens of AIDS patients. The most common cancer seen in this study were malignant lymphomas (4% of cases) with development of extensive extranodal lymphomatous involvement from the outset. Although a preponderance of high grade B-cell pathologic subtypes is found in AIDS-associated lymphoma, we also report the first case of T-lymphoblastic lymphoma with a picture of acute lymphoblastic leukemia (T-ALL). Tuberculosis (34% of cases) was the most common opportunistic infection presented in tissue sections, and the majority of tissue biopsies revealed poorly organized granulomas and extensive necrosis with numerous bacilli. Penicilliosis (20% of cases) appeared to be the most common cutaneous lesion with multiple organ involvement. The involved organs showed a partially anergic tissue reaction characterized by poorly formed granulomas with diffuse infiltrate of fungi-laden macrophages and lymphoid cell depletion. This organism has to be distinguished from Histoplasma capsulatum and other yeast-form fungi. Co-existing cytomegalovirus and P. carinii infections were the predominant findings in lung necropsy specimens from pediatric patients who died from AIDS. A major pathologic feature in this group was diffuse alveolar damage stage II to III with heavy loads of organism and extensive lymphoplasmacytic infiltration.