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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult T-cell leukemia (ATL) is a human T-cell leukemia virus type I (HTLV-I)-infected lymphoproliferative disorder that shows a characteristic nodular infiltration into various tissues, hypercalcemia, and subsequent rapid increase of peripheral ATL cell number. ATL cells and HTLV-I-infected T-cell lines also make cluster formation rapidly after the non-stimulative culture. However, the mechanism of the acute proliferation of ATL cells remains to be understood. We report the following novel features of homotypic adhesion via leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pathway that suggest a role for it in cytokine production and rapid proliferation of ATL cells: (1) ATL cells show clustering in a calcium dependent manner, even at the higher concentration; (2) ATL cells consistently and highly express ICAM-1 and an active form of LFA-1, whereas integrin expression, except for LFA-1, is rather lower compared with that of normal CD4+ T cells; (3) ATL cells make conjugate formation within 6 minutes and clustering within 48 hours, both of which are inhibited by the addition of monoclonal antibodies (MoAbs) against LFA-1 and ICAM-1; (4) spontaneous mRNA transcription and protein secretion of both interleukin-1 and parathyroid hormone-related protein are observed consistently in ATL cells, and these productions are inhibited by anti-LFA-1 and anti-ICAM-1 MoAbs but are markedly increased by cross-linking of LFA-1 and ICAM-1 by the immobilized specific MoAbs; and (5) proliferative responses of ATL cells are also inhibited by these MoAbs. We propose that ATL cells proliferate in sequential events: the homotypic and calcium-dependent adhesion through LFA-1/ICAM-1, the signal transduction through these adhesion molecules, the production of cytokines, and the proliferation.
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PMID:Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro. 766 73

Adult T-cell leukemia (ATL) associated with HTLV-1 infection is characterized by the development of hypercalcemia in over two thirds of patients. Dysregulation of cellular gene transcription by viral proteins is an emerging paradigm for molecular pathogenesis of disease. A recent example is the parathyroid hormone-related protein (PTHrP) gene, which has been implicated in the hypercalcemia of ATL, and is transactivated by the HTLV-1 tax and HTLV-11 tax proteins. PTHrP is expressed at high levels in leukemia cells derived from ATL patients, as well as in asymptomatic HTLV-1 positive carriers. This article reviews the interaction of the HTLV-1 transcriptional regulator tax with the PTHrP promoter. Tax mediates its effects on PTHrP via cellular transcription factors AP-2 and AP-1, and transactivation via an AP-2 motif represents a novel interaction of tax with a cellular transcription factor.
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PMID:Hypercalcemia, parathyroid hormone-related protein expression and human T-cell leukemia virus infection. 781 98

We analyzed the serum levels of C-terminal parathyroid hormone-related protein (C-PTHrP) in asymptomatic carriers of human T lymphotropic virus type 1 (HTLV-1) and patients with three HTLV-1 related diseases; adult T-cell leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU). Serum C-PTHrP levels were significantly elevated in HTLV-1-infected individuals, irrespective of whether they were symptomatic or asymptomatic, when compared with that of the seronegative controls. In ATL patients, a good correlation was demonstrated between the serum C-PTHrP level and serum calcium or lactic dehydrogenase (LDH) level. Thus the elevated serum C-PTHrP level could be a characteristic marker of HTLV-1 carrier state, and the determination of its level in ATL patients could be useful for the assessment of the prognosis and as one of the tumor markers. The determination of the serum level of C-PTHrP in various stages of the HTLV-1 carrier state would help to understand the mechanism of the development of hypercalcemia in ATL.
Leukemia 1994 Oct
PMID:Increased serum levels of C-terminal parathyroid hormone-related protein in different diseases associated with HTLV-1 infection. 793 67

Hypercalcaemia is common in some lymphoproliferative disorders such as myeloma or T-cell leukaemia-lymphoma, but is rarely described in B cell chronic lymphocytic leukaemia (BCLL). We report the case of a patient with BCLL, hypercalcaemia and osteolytic bone lesions. Parathyroid hormone-related protein (PTHrP) mRNA was identified by Northern blot analysis of liver, spleen and lymph node tumour samples. Serum levels of tumour necrosis factor alpha (TNF alpha) were increased.
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PMID:Hypercalcaemia in B cell chronic lymphocytic leukaemia. 773 84

A retrospective study of 26 adults with acute T-cell leukemia showed that 14 patients (54%) had hypercalcemia at some point of the disease. Hypercalcemia was found at presentation in nine patients and revealed the disease in one. Eight patients had hypercalcemia at the time of death. Serum phosphorus and parathyroid hormone levels were normal. All patients with hypercalcemia tested positive for the HTLV-1 by Elisa and Western blot. Six patients had focalized or diffuse lytic roentgenographic bone lesions. Hypercalcemia in acute T-cell leukemia may involve production of interleukin-1-alpha and parathyroid hormone-related protein by HTLV-1-infected cells.
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PMID:[Hypercalcemia of T-cell leukemia in adults]. 816 27

Expression of the parathyroid hormone-related protein (PTHrP), a protein that plays a primary role in the development of the humoral hypercalcemia of malignancy, is regulated by two distinct promoters, P1 and P2. PTHrP is overexpressed in lymphocytes from adult T-cell leukemia patients. We now demonstrate that in the human T-cell lymphotropic virus type I-transformed cell line MT-2, RNA synthesis is initiated primarily at the P2 promoter. Furthermore, in cotransfection experiments, Tax1 transactivates the P2 promoter 10- to 12-fold. By using deletion and site-specific point mutations, we have identified a promoter-proximal sequence (positions -72 to -40) which is important for Tax1 transactivation. The PTHrP promoter-proximal element contains two potential overlapping Ets1 binding sites, EBS I and EBS II. Gel shift analysis demonstrated that Ets1 binds specifically to both EBS I and EBS II. Mutation of the consensus GGAA core motif in EBS I abolished binding and Tax1 transactivation in Jurkat T lymphocytes. In Ets1-deficient cells, cotransfection of Tax1 and Ets1 expression plasmids stimulates PTHrP promoter activity. In the absence of Ets1, minimal transactivation of the PTHrP promoter is observed. These data suggest that Ets1 binds to EBS I and cooperates with Tax1 to transactivate the PTHrP P2 promoter.
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PMID:Transactivation of the P2 promoter of parathyroid hormone-related protein by human T-cell lymphotropic virus type I Tax1: evidence for the involvement of transcription factor Ets1. 837 55

We describe a case of hypercalcemia without lytic bone lesions complicating myeloid blast crisis of chronic myeloid leukemia (CML). Serum levels of parathyroid hormone-related protein (PTHrP) were elevated during the initial hypercalcemic period and became undetectable during chemotherapy-induced chronic phase, only to become elevated again during subsequent recurrent blastic periods repeatedly associated with hypercalcemia. Previously reported cases of hypercalcemia complicating CML are reviewed. It is suggested that PTHrP was responsible for the hypercalcemia in this case and may be an important mediator of hypercalcemia in CML.
Leukemia 1993 Oct
PMID:Hypercalcemia in the blastic phase of chronic myeloid leukemia associated with elevated parathyroid hormone-related protein. 841 32

The human T-cell leukemia virus type I (HTLV-I) and HTLV-II Tax proteins are potent transactivators of viral and cellular gene expression. Using deletion mutants, the downstream parathyroid hormone-related protein (PTHrP) promoter is shown to be responsive to both HTLV-I and HTLV-II Tax as well as the AP1/c-jun proto-oncogene. Transactivation of PTHrP by Tax was seen in T cells but not in B-cell lines or fibroblasts. A carboxy terminal Tax deletion mutant was deficient in transactivation of both the PTHrP and IL2R alpha promoters but not the HTLV-I long terminal repeat (LTR). Exogenous provision of NFkB rescued IL2R alpha expression but not the PTHrP promoter. Thus, HTLV-I Tax, HTLV-II Tax, and c-jun transactivate PTHrP and may contribute to the pathogenesis of hypercalcemia in adult T-cell leukemia.
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PMID:Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type I (HTLV-I) tax and HTLV-II tax proteins. 842 83

Leukemic cells from patients with adult T-cell leukemia (ATL) can produce a calcium-regulating protein, parathyroid hormone-related protein (PTHrP). Moreover, it has been reported that ATL cells produce some cytokines besides PTHrP and that these cells respond to the T-cell growth factors, interleukin-2 (IL-2) and interleukin-4 (IL-4). To elucidate whether PTHrP produced by ATL cells is regulated by IL-2 or IL-4, we investigated the in vitro effects of IL-2 and IL-4 on the release of PTHrP. IL-2 increased the release of PTHrP into the conditioned medium from leukemic cells in some, but not all, ATL patients; however, IL-4 did not affect the PTHrP release. PTHrP messenger RNA (mRNA) levels were increased in ATL cells cultured in the presence of IL-2. These data suggest that IL-2 plays a role in the regulation of hypercalcemia by enhancing the production of PTHrP in ATL patients.
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PMID:Enhancing effect of interleukin-2 on production of parathyroid hormone-related protein by adult T-cell leukemia cells. 851 9

A 44 year old Japanese woman with adult T-cell leukaemia (ATL) was admitted to Kyushu University hospital to receive a course of alpha-interferon treatment. She experienced a sudden onset of hypercalcaemia and epigastric pain associated with an increase in the level of pancreatic enzymes. Her serum parathyroid hormone related protein level was above normal although her high sensitive PTH level was within the normal range. Ultrasonography and computed tomography (CT) of the abdomen showed enlargement of the pancreas with indistinct margins and massive accumulation of extrapancreatic fluid. Cullen's sign was observed. A few days after the onset of acute pancreatitis, the serum amylase level increased to 3400 IU/L, and the serum calcium level fell to 4.2 mg/dL from 13.3 mg/dl. Her fasting blood glucose level increased to 242 mg/dL. Although the first episode of pancreatitis appeared to respond to treatment, she experienced a second episode of pancreatitis accompanied by an elevation of the serum calcium level. These findings suggest that acute pancreatitis was caused by hypercalcaemia associated with ATL.
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PMID:Acute pancreatitis induced by hypercalcaemia associated with adult T-cell leukaemia: a case report. 867 68


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