The spectrum of metabolic bone disease in lymphoblastic leukemia

Cohn, Susan L.; Morgan, Elaine; Mallette, Lawrence E.

doi:10.1002/1097-0142(19870115)59:2<346::aid-cncr2820590230>3.0.co;2-i

Cited by 41 publications

(11 citation statements)

References 26 publications

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“…and varied from weakly (Figure lb tor a metabolism have all been proposed (Cohn et al, 1987;Kiyokawa et al, 1987;Fukumoto et al, 1988;Adams et al, 1989;Matsuda et al, 1990). Recent studies have suggested a role for PTHrP, a new parathyroid hormone-like protein (Suva et al, 1987;Mangin et al, 1988) which is involved in normal calcium homeostasis in the foetus and implicated in the development of humoral hypercalcaemia of malignancy syndrome seen associated with epithelial tumours Danks et al, 1989;Burtis et al, 1990;and reviewed in Martin & Suva, 1989;Kelly & Eisman, 1989).…”

Section: Resultssupporting

confidence: 85%

“…Abnormalities in parathyroid hormone, prostaglandin E and vitamin D metabolism have been suggested, but investigation of a large series of cases of ATLL has failed to demonstrate significant abnormalities (Cohn et al, 1987;Kiyokawa et al, 1987;Fukumoto et al, 1988). Recent studies have implicated a role for the hypercalcaemia-associated parathyroid hormone related protein (PTHrP) (Suva et al, 1987;Mangin et al, 1988) in the generation of hypercalcaemia in ATLL.…”

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confidence: 99%

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Immunocytochemical demonstration of PTHrP protein in neoplastic tissue of HTLV-1 positive human adult T cell leukaemia/lymphoma: implications for the mechanism of hypercalcaemia

Moseley

Danks²,

Grill³

et al. 1991

Br J Cancer

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Summary The infiltrated tissues from seven West Indian patients with HTLV-1 positive adult T cell lymphoma/leukaemia (ATLL) have been analysed by immunocytochemical techniques for the presence of immunoreactive parathyroid hormone-related protein (PTHrP), a hormonal mediator of humoral hypercalcaemia of malignancy. Six of the seven were hypercalcaemic at some stage of the course of their disease. Four of the six evaluable patients showed evidence of specific cellular and extracellular expression of PTHrP protein in neoplastic tissues. This finding suggests that PTHrP may be involved in the production of hypercalcaemia in at least some cases of T cell lymphoma -proof of a causal relationship however must await the demonstration of tissue release of PTHrP resulting in raised circulating hormone levels.Adult T cell lymphoma/leukaemia (ATLL) (reviewed in Uchiyama, 1988;Neely, 1989) is a neoplasm of lymphocytes presumptively caused by the human T cell lymphotropic virus, HTLV-1, (Yamaguchi et al., 1984) and exhibiting a characteristic morphology. It has a pronounced geographical distribution originally being described in south-western Japan (Uchiyama et al., 1977) and later also shown to have a particular prevalance in Caribbean emigrants to the UK and USA (Catovsky et al., 1982;Blayney et al., 1983;Bunn et al., 1983;Swerdlow et al., 1984). The disease is frequently associated with hypercalcaemia, which taken with its resistance to chemotherapy, contributes to the uniformly poor prognosis.The aetiology of hypercalcaemia in ATLL has not been fully elucidated. Abnormalities in parathyroid hormone, prostaglandin E and vitamin D metabolism have been suggested, but investigation of a large series of cases of ATLL has failed to demonstrate significant abnormalities (Cohn et al., 1987;Kiyokawa et al., 1987;Fukumoto et al., 1988). Recent studies have implicated a role for the hypercalcaemia-associated parathyroid hormone related protein (PTHrP) (Suva et al., 1987;Mangin et al., 1988) in the generation of hypercalcaemia in ATLL. Motokura et al. (1988) have demonstrated elevated levels of PTHrP mRNA and secretion of PTHrP from a cell line MT-2, derived from a case of ATLL. More recently, PTHrP protein has been isolated from leukaemic effusions in two patients with ATLL (Motokura et al., 1989) and peripheral blood of another . It has also been reported that a dog lymphosarcoma, capable of inducing hypercalcaemia upon transplantation (Weir et al., 1988), has raised PTHrP mRNA levels.In this study we have localised PTHrP in ATLL by immunocytochemical techniques using a series of antibodies to synthetic peptides derived from the N-terminal and Cterminal segments of PTHrP. Table I.Standard histopathology, formalin-fixed wax-embedded, biopsy material was used for immunohistological analysis.All was archival and had not been prepared especially for the study; of note, tissue fixation times (ideally less than 24 h for detection of PTHrP) may have been prolonged, particularly with the marrow trephine biopsy samples. All available biop...

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Section: Resultssupporting

confidence: 85%

mentioning

confidence: 99%

Immunocytochemical demonstration of PTHrP protein in neoplastic tissue of HTLV-1 positive human adult T cell leukaemia/lymphoma: implications for the mechanism of hypercalcaemia

Moseley

Danks²,

Grill³

et al. 1991

Br J Cancer

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“…Musculoskeletal pain has been reported in 36% of children at the time of diagnosis of acute leukemia and lymphoma [6,7,9]. Diffuse osteopenia and vertebral fractures are observed in 1-24% before therapy is initiated [6][7][8].…”

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confidence: 99%

“…Diffuse osteopenia and vertebral fractures are observed in 1-24% before therapy is initiated [6][7][8].…”

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confidence: 99%

Low Bone Mass in Children With Malignant Lymphoma

El-Ziny

Al‐Tonbary

Salama

et al. 2007

Pediatric Hematology and Oncology

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The aim of this work was to study the effect of disease process on bone mass and calcium homeo-stasis in children with malignant lymphoma at diagnosis, 3 months after starting chemotherapy, and after 1 year. Evaluation of lumber vertebrae (L2-L4) bone mineral density using dual-energy X-ray absorptiometry and calcium homeostasis parameters and bone turnover biochemical markers (serum osteocalcin and urinary deoxypyridinoline) had been assayed in twenty lymphoma patients at presentation and after treatment. Low bone mass for chronological age was observed in 4 patients (20%) at diagnosis and persisted after 3 months and 1 year. Parathyroid hormone level demonstrated no differences between children with lymphoma at different stages of therapy and controls, while 25(OH) D(3) was significantly lower in lymphoma patients at different stages of therapy as compared to controls (p < .001). Osteocalcin was significantly lower in lymphoma patients at different stages of therapy. Deoxypyridinoline showed only significant higher values after 3 months of therapy compared to controls (p = .01). In conclusion, low bone mass was observed in children with lymphoma and is related to decreased osteoblastic activity and decreased mineralization of bone.

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“…Acute lymphoblastic leukemia (ALL) can rarely present with hypercalcemia, osteolytic lesions, and absence of circulating blasts [1] Hypercalcemia complicating malignancy is a frequent complication in adult patients, with an incidence up to 20% [2] Among hematopoietic malignancies, multiple myeloma and T-cell leukemia/lymphoma have a high incidence of this metabolic abnormality; on the other hand, only a few cases of ALL with hypercalcemia have been reported in children [3][4][5][6][7][8].…”

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confidence: 99%

A Case of Acute Lymphoblastic Leukemia Presenting as Sever Hypercalcemia

Buonuomo

Ruggiero

Piastra

et al. 2004

Pediatric Hematology and Oncology

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A 9-year-old girl presented at the Pediatric Emergency Department with an acute onset of gastrointestinal symptoms due to hypercalcemia. Despite the absence of circulating blast, bone marrow biopsy was diagnostic of acute lymphoblastic leukemia. The hypercalcemia was initially treated with intravenous hydration and furosemide, and later on with bisphosphonates. However, the serum calcium levels normalized only after the beginning of specific chemotherapy. Hypercalcemia represents an emergency in children, and acute leukemia must be considered in its differential diagnosis, even when there are no circulating blasts.

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The spectrum of metabolic bone disease in lymphoblastic leukemia

Cited by 41 publications

References 26 publications

Immunocytochemical demonstration of PTHrP protein in neoplastic tissue of HTLV-1 positive human adult T cell leukaemia/lymphoma: implications for the mechanism of hypercalcaemia

Immunocytochemical demonstration of PTHrP protein in neoplastic tissue of HTLV-1 positive human adult T cell leukaemia/lymphoma: implications for the mechanism of hypercalcaemia

Low Bone Mass in Children With Malignant Lymphoma

A Case of Acute Lymphoblastic Leukemia Presenting as Sever Hypercalcemia

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