title: Acute lymphocytic leukemia in adolescence with multiple osteolytic lesions and hypercalcemia mediated by lymphoblast-producing parathyroid hormone-related peptide: a case report and review of the literature.
abstract: BACKGROUND
  Osteopathy is one of the common initial symptoms of acute lymphocytic leukemia (ALL) in children and adolescents, but multiple osteolysis accompanied by hypercalcemia is rarely observed.
  
  
  METHODS
  We treated a 14-year-old female who had multiple osteolytic lesions and hypercalcemia at initial onset of ALL. In this case we examined some humoral factors, which are known to associate with hypercalcemia in malignancies.
  
  
  RESULTS
  Parathyroid hormone-related peptide (PTHrP) was elevated in serum, and reverse transcriptase-polymerase chain reaction and immunohistochemistry revealed that the lymphoblasts produced PTHrP directly. Other humoral factors related to hypercalcemia were not detected. ALL relapsed in the bone marrow 3 months after achieving complete remission, and hypercalcemia and elevation of serum PTHrP were also observed. A second remission could not be achieved and hypercalcemia continued. The patient received allogeneic bone marrow transplantation. The serum calcium level became normal after the conditioning therapy. Before engraftment, however, the patient died of infection.
  
  
  CONCLUSIONS
  The present case suggests that blast-producing PTHrP might be associated with multiple osteolytic lesions and hypercalcemia. PTHrP expressed in the lymphoblasts may, in itself, confer a survival advantage to lymphoblasts and contribute to the refractory nature of the disease.
authors.affiliation: Section of Pediatrics, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Shimonodan
authors.forename: Jun
authors.initials: J
authors.lastname: Nagayama
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nagatoshi
authors.forename: Michiki
authors.initials: M
authors.lastname: Hatanaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Takada
authors.forename: Haruo
authors.initials: H
authors.lastname: Iguchi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
mesh_terms: D000293:Adolescent; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000209:etiology*; D010014:Osteolysis / Q000097:blood / Q000209:etiology*; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000150:complications*; D012008:Recurrence
chemical_list: D044162:Parathyroid Hormone-Related Protein