PTHrP-independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19-negative precursor B acute lymphoblastic leukemia.
Hypercalcemia in childhood acute lymphoblastic leukemia (ALL) is rare and occasionally associated with parathyroid hormone-related protein (PTHrP). However, the pathogenesis of PTHrP-independent hypercalcemia remains unclear. We report two children with precursor B ALL who had marked hypercalcemia (15.8 and 16.6 mg/dl, respectively) and disseminated osteolysis. Serum tumor necrosis factor-alpha (TNF-alpha) and IL-6 were markedly elevated, whereas 1,25(OH)(2) vitamin D(3), intact PTH and PTHrP were decreased or undetected. Analysis of urinary deoxypyridinoline (DPY) or bone biopsy of the osteolytic lesion showed an increased bone resorption, and administration of bisphosphonate improved the hypercalcemia. Patients had ALL with immunophenotype positive for CD10, CD34, and HLA-DR but negative for CD19 and obtained remission with chemotherapy. These findings suggest that increased osteoclastic bone resorption via stimulation with TNF-alpha and IL-6 may be mechanism causing PTHrP-independent hypercalcemia in some patients with precursor B ALL lacking CD19 expression.
Department of Pediatrics, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
Hidetaka
H
Niizuma
Kunihiro
K
Fujii
Atsushi
A
Sato
Ikuma
I
Fujiwara
Junji
J
Takeyama
Masue
M
Imaizumi
D000596:Amino Acids / Q000032:analysis / Q000652:urine; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D001862:Bone Resorption / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D016130:Immunophenotyping; D008297:Male; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D012074:Remission Induction; D016896:Treatment Outcome
D000596:Amino Acids; D050071:Bone Density Conservation Agents; D016207:Cytokines; D004164:Diphosphonates; D044162:Parathyroid Hormone-Related Protein; C036020:deoxypyridinoline