Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Full skeletal survey was performed on 193 consecutive children presenting over a 6-year period with acute lymphoblastic leukaemia (ALL). A record was made of the degree of bone pain in these patients and 60 others presenting immediately prior to the availability of skeletal surveys. Bone pain was present in 76 out of 253 patients (30%) and radiological bone changes characteristic of leukaemia in 125 out of 193 (65%). A significant correlation was found between the severity of bone pain and the number of bones involved on X ray (r = 0.25, P = less than 0.001), but not between initial white cell counts and bone score (r = -0.14, P = 0.08). There was no significant correlation between the degree of bone pain and survival or length of first remission (P = 0.29 and 0.86). Similarly, the extent of radiological bone disease was of no prognostic significance with relation to survival (P = 0.41) or length of first remission (P = 0.21).
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PMID:The prognostic significance of radiological and symptomatic bone involvement in childhood acute lymphoblastic leukaemia. 28 56

N-tropic murine leukemia viruses have been observed in connection with radiation-induced osteosarcomagenesis in BALB/c mice. We have investigated the bone disease-inducing potential of molecularly cloned, BALB/c-derived N-tropic viruses in the random-bred NMRI mouse strain. The germ-line virus and an exogenous virus isolate were found to induce high incidences of osteopetrosis and lymphomas and a lower incidence of osteomas. Two viruses derived from somatically acquired proviruses of independent radiation-induced osteosarcomas induced lower incidence of osteopetrosis and lymphomas. Nucleotide sequence analysis of the long terminal repeat regions and RNase T1 fingerprint analysis revealed only few differences between the isolates. The possible involvement of N-tropic murine leukemia viruses in radiation-induced osteosarcomagenesis in the BALB/c mouse strain is discussed.
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PMID:Pathogenicity of BALB/c-derived N-tropic murine leukemia viruses. 217 70

There are two sources of vitamin D available to man: The more important source is the cholecalciferol (vitamin D3), which is produced photochemically in the skin from the provitamin, 7-dehydrocholesterol; vitamin D ingested with food is of secondary importance, but assumes a critical role when an individual is deprived of solar exposure. Vitamin D therefore is not strictly a vitamin. A deficiency of vitamin D ultimately results in osteomalacia in adults and rickets in children, and provision of sunlight or small oral doses of the vitamin can cure this bone condition. There are, however, many less common conditions in which small doses of the vitamin are ineffective, whereas larger doses of vitamin D can achieve healing of the bone disease. These conditions are collectively called vitamin D-resistant diseases and include hypoparathyroidism, genetic and acquired hypophosphataemic osteomalacias, renal osteodystrophy, vitamin D-dependent rickets, and the osteomalacia associated with liver disease and intestinal malabsorption. Unfortunately, large doses of vitamin D continue to be prescribed for a wide variety of diseases in which there is little scientific evidence of their efficacy. The benefits and dangers of high doses of vitamin D are discussed and the problems arising from inappropriate or poorly supervised treatment with vitamin D presented. The serum concentration of the active metabolite of vitamin D, 1,25 dihydroxyvitamin D is increased in certain disease states, and the pathophysiology of some these diseases are presented. The exciting developments in tumour differentiation and the role of high doses of 1,25 dihydroxyvitamin D for the control of leukaemia and other blood and skin diseases are discussed.
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PMID:High-dose vitamin D therapy: indications, benefits and hazards. 250 9

Adult T cell leukaemia/lymphoma was first identified by Japanese investigators in the mid 1970s. Distinctive characteristics include hypercalcaemia, metabolic bone disease, opportunistic infections and evidence of multiorgan involvement. The malignant cell has the surface phenotype of a T helper lymphocyte but functions as a T suppressor cell, and in leukaemic patients this cell usually has a unique multilobed appearance, which may aid in recognizing the disease. The overwhelming majority of patients with ATLL originate from the south-west Japanese archipelago, as well as the Caribbean basin and south-east USA. The geographic localization of this disease is the result of the endemic distribution of the human retrovirus (HTLV-I) which has been established as the cause of ATLL. Infection with this virus may result in no disease (asymptomatic carriers) or ATLL. While ATLL usually pursues an acute or subacute (prototypic) course, patients are also seen with 'chronic' or 'smouldering' disease. Over time, these more indolent variations may progress to the prototypic form. When aggressive, ATLL must be treated with intense combinations of cytotoxic drugs similar to those used to treat the more common B cell lymphoproliferative disorders. Even though half of the patients treated achieve a remission, the duration is usually brief and the overall actuarial median survival is only 11 months. In addition to recurrent disease, these patients frequently succumb to opportunistic infections.
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PMID:Adult T cell leukaemia/lymphoma. 287 62

Two adults who had T-cell lymphoma-leukemia and recurrent hypercalcemia in the absence of radiographic evidence of bone disease are described. Bone histopathology showed marked osteoclastic activation. Bone resorbing factors, including both prostaglandin E and a material produced in the presence of a prostaglandin synthetase inhibitor, were detected in the in-vitro culture fluids of malignant cells of one of the patients. Serum levels of parathyroid hormone were not elevated. These findings suggest that hypercalcemia resulted from in-vitro osteoclast activation by tumor cell product(s), one of which may be similar, if not identical, to the lymphocyte product osteoclast-activating factor. Two other patients having T-cell lymphoma-leukemia and hypercalcemia have been identified in the literature: the malignant cells of one of these patients also released a calcium-mobilizing factor in vitro.
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PMID:Hypercalcemia associated with T-cell lymphoma-leukemia. 697 May 19

From October 1983 until December 1988, 50 patients with asymptomatic multiple myeloma stage I were included in a prospective randomized multi-centre study comparing melphalan-prednisone (MP) therapy started at the time of diagnosis with deferred therapy where MP was started at the time of disease progression. Twenty-five patients were randomized to each group. The median time from diagnosis to start of therapy in the group with deferred therapy was 12 months. The reasons for starting therapy were increasing M-protein in 8 cases, symptomatic bone disease in 9 and anaemia in 5. In 2 cases, disease progression was complicated by vertebral fractures necessitating radiotherapy. Two patients in the group in which MP was started at the time of diagnosis developed acute leukaemia. No differences in response rate, response duration or survival were observed between the treatment groups. We conclude that in asymptomatic myeloma deferral of chemotherapy is feasible in well-informed and well-controlled patients but conveys no advantage in survival. In clinical practice the benefits of treatment deferral are to some extent outweighed by disease progression before start of treatment.
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PMID:Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Myeloma Group of Western Sweden. 844 Mar 64

PEBP2/CBF is a heterodimeric transcription factor composed of alpha and beta subunits. There are at least three closely related genes, PEBP2alphaA/Cbfa1, AML1/PEBP2alphaB/Cbfa2 and PEBP2alphaC/Cbfa3, encoding the alpha subunit and one beta subunit encoding gene. Structural alterations of AML1 and the beta subunit gene by chromosome translocations are frequently associated with several types of human leukemia. Structural changes of any of these gene products would have potential to affect the function of others. In this study, we isolated the human PEBP2alphaA cDNA by which we mapped the gene to 6p12.3-p21.1. Human chromosome 6p21 is the locus for cleidocranial dysplasia, an autosomal dominant bone disease. Recent gene disruption study revealed that PEBP2alphaA/Cbfa1 plays an essential role in osteogenesis (Komori et al., Cell, 1997, in press). Therefore, a close relationship between human PEBP2alphaA/CBFA1 and this bone disease is strongly implicated.
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PMID:The cDNA cloning of the transcripts of human PEBP2alphaA/CBFA1 mapped to 6p12.3-p21.1, the locus for cleidocranial dysplasia. 923 71

The optimal management of hematopoietic malignancies in the elderly requires the development of specific therapeutic strategies based on the peculiar clinico-biologic features of aged patients. Multiple myeloma arising in elderly patients remains at this time an incurable disease, while attention to supportive therapy and palliation can make a great impact on the quality of life. Fortunately advances have been made in last years in this field. Therapy at the time of diagnosis is usually recommended for patients with symptomatic disease, or for those who may be asymptomatic, but have evidence of high tumor burden of a biologically aggressive disease, and may be expected to progress and develop complications over a short period of time. Melphalan combined with prednisone remains the standard therapy choice in elderly patients. Radiotherapy maintains an important place in the palliation of destructive bone disease in poorly controlled myeloma, particularly in elderly patients. In Acute Myelogenous Leukemia, age has been concordantly reported as an adverse prognostic indicator in affecting both remission rates and survival. The overall unsatisfactory therapeutic results appear connected with host-related factors, and intrinsic differences in the biology of leukemia. Patients with standard risk should be included in collaborative trials aimed at improving the long-term results of conventional therapy. Patients with high risk and unfavorable prognostic factors, could be enrolled in controlled studies aimed at better assessing, in the elderly, the long term results of newer drug combinations. A watch and wait strategy, consisting of transfusion support and leukocytosis control, should be limited to patients with extremely poor performance status (PS), very limited life-expectancy and/or severe comorbidity displaying unfavorable biologic factors, including secondary Acute Myelogenous Leukemia.
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PMID:Treatment of multiple myeloma and acute myelogenous leukemia in the elderly: an update. 925 11

In a double blind randomized study, the bisphosphonate drug Pamidronate (Aredia) significantly protected Durie-Salmon stage III multiple myeloma patients from osteolytic bone disease. In the patient sub-group on salvage chemotherapy. Pamidronate treatment was also significantly associated with prolonged survival. To test if this drug could induce direct antitumor effects, we exposed myeloma cells to increasing concentrations of Pamidronate or a more potent bisphosphonate, Zoledronate. A concentration- and time-dependent cytotoxic effect was detected on four of five myeloma cell lines as well as three specimens obtained directly from myeloma patients. Zoledronate-induced cytotoxicity was significantly greater than that of Pamidronate. Cytotoxicity could not be explained by bisphosphonate-induced chelation of extracellular calcium or secondary decrease in production of the myeloma growth factor interleukin-6. Morphological examination, DNA electrophoresis and cell cycle analysis indicated that the bisphosphonate-induced cytotoxic effect consisted of a combination of cytostasis and apoptotic myeloma cell death. Enforced expression of BCL-2 protected against the apoptotic death but not against cytostasis. Most cytotoxic effects were seen between 10 and 100 microM of drug. The results suggest a possible direct anti-tumor effect in myeloma patients treated with bisphosphonates which may participate in their significantly increased survival. This hypothesis should now be further tested in clinical trials.
Leukemia 1998 Feb
PMID:In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates. 951 85

Low bone density in growing girls and mature young women is usually a finding that needs an explanation and further clinical investigation. Population-based epidemiologic studies on osteoporosis in young persons do not exist. As a disease, osteoporosis among children and adolescents is rate, and since 1965 only 100 cases of idiopathic juvenile osteoprososis have been reported. When osteoporosis occurs in children, it is usually secondary to an underlying medical disorder (e.g., anorexia nervosa, leukemia) or to medications, but occasionally no identifiable primary cause can be detected. It may also be the result of a genetic disorder such as osteogenesis imperfecta. On the other hand, osteopenia in growing and young persons seems much commoner and needs further investigation. Adolescence is a period of increased calcium requirement, and girls with an underlying bone disease are at higher risk for bone demineralization. An additional point of interest is the changes in the geometry of bones through their continuous adaptation to simultaneous skeletal and muscular growth. Bones, through the mechanostat mechanism, adapt to mechanical loading by differentiating their geometry. A recent finding in this direction is that before and during the teenage years there is an environmental effect of physical activity and nutrition on hip geometry. Another important finding is an age-dependent increase in bone cross-sectional area and bone strength index in the absence of an increase in volumetric spongiosa bone density and cortical bone density. Girls, in comparison to boys, deposit more calcium in their bones during puberty, thus probably preparing their skeleton for the forthcoming events of pregnancy and lactation.
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PMID:Osteopenic syndromes in the adolescent female. 1081 28


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