{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T01:03:22Z","timestamp":1782003802408,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,2,22]],"date-time":"2006-02-22T00:00:00Z","timestamp":1140566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypercalcemia in childhood acute lymphoblastic leukemia (ALL) is rare and occasionally associated with parathyroid hormone\u2010related protein (PTHrP). However, the pathogenesis of PTHrP\u2010independent 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\u2010\u03b1 (TNF\u2010\u03b1) and IL\u20106 were markedly elevated, whereas 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub>, 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\u2010DR but negative for CD19 and obtained remission with chemotherapy. These findings suggest that increased osteoclastic bone resorption via stimulation with TNF\u2010\u03b1 and IL\u20106 may be mechanism causing PTHrP\u2010independent hypercalcemia in some patients with precursor B ALL lacking CD19 expression. Pediatr Blood Cancer 2007;49:990\u2013993. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/pbc.20782","type":"journal-article","created":{"date-parts":[[2006,2,22]],"date-time":"2006-02-22T19:16:26Z","timestamp":1140635786000},"page":"990-993","source":"Crossref","is-referenced-by-count":26,"title":["PTHrP\u2010independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19\u2010negative precursor B acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"49","author":[{"given":"Hidetaka","family":"Niizuma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuma","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Takeyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masue","family":"Imaizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,2,22]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19930701)72:1<256::AID-CNCR2820720145>3.0.CO;2-D"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.45.1.189"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-5710(97)00052-2"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.69.812.483"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0037-1963(01)90020-4"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.2.634"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19971015)80:8 <1557::AID-CNCR5>3.0.CO;2-H"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010801)92:3<460::AID-CNCR1344>3.0.CO;2-D"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1190"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.38.1.375"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/sonc.2002.37417"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000615)88:12 <2979::AID-CNCR13>3.0.CO;2-U"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067518"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.10.3551.422k08_3551_3558"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-200X.2003.01665.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-199305000-00013"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1997.tb14807.x"},{"key":"e_1_2_6_19_2","first-page":"364","article-title":"Tumor necrosis factor\u2010\u03b1 in malignant disease","volume":"15","author":"Abrahamsson J","year":"1993","journal-title":"Am J Pediatr Hematol Oncol"},{"key":"e_1_2_6_20_2","first-page":"101","article-title":"The IL\u20106 gene expression by leukemic cells from acute lymphoblastic leukemia common and T type and modulation of IL\u20106 production by TNF","volume":"29","author":"Pituch\u2010Noworolska A","year":"1998","journal-title":"Hematologica"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-9883"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-200108000-00009"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-124-3-1424"},{"key":"e_1_2_6_24_2","first-page":"546","article-title":"The role of interleukin\u20106 and interleukin\u20106\/interleukin\u20106 receptor\u2010alpha complex in the pathogenesis of multiple myeloma","volume":"11","author":"Barille S","year":"2000","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2000.90074.x"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.8.1486"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.201394498"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190290012146"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20063"}],"container-title":["Pediatric Blood &amp; 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