Elucidation of the N- cadherin molecular mechanism in the leukemia microenvironment in bone marrow and the central nervous system

• Project/Area Number: 24591546
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Mie University
• Principal Investigator: IWAMOTO Shotaro 三重大学, 医学部附属病院, 助教 (20456734)
• Co-Investigator(Kenkyū-buntansha): HIRAYAMA Masahiro 三重大学, 医学系研究科, 准教授 (90293795)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: N-カドヘリン / 白血病微小環境 / 急性白血病 / 骨髄白血病微小環境 / Ｎ－ｃａｄｈｅｒｉｎｅ / ＢＭ ｎｉｃｈｅ / ＣＮＳ ｎｉｃｈｅ / Ｌｅｕｋｅｍｉａ

Outline of Final Research Achievements

N-cadherin, a family of Ca2+-dependent intercellular adhesion molecules, plays key roles in controlling morphogenetic movements during development and hematopoiesis in bone marrow (BM). Recently, it has been reported that this molecule might be associated with drug resistance in adult leukemia. Then we studied the clinical significance of N-cadherin in BM niche in acute childhood leukemia.
We found that N-cadherin was highly expressed on primary / hTERT immortalized BM stroma cells (BMSCs). Several kinds of leukemic cell lines and primary childhood leukemia cells also expressed different levels of N-cadherin. In addition, drug sensitivity in leukemic cells for anti-leukemic agents in co-culture system between leukemic cells and BMSCs increased in the presence of GC-4 antibody that can inhibit N-cadherin adherens junction formation .Taken together, these results supported that N-cadherin might be related to drug resistance in childhood acute leukemic cells in BM microenvironments.

Research Products

• [Journal Article] Anaphylactic transfusion reaction in homozygous haptoglobin deficiency detected by CD203c expression on basophils. (2014)
  • Author(s): Iwamoto S, Yonekawa T, Azuma E, Fujisawa T, Nagao M, Shimada E, Nakamura R, Teshima R, Ohishi K, Toyoda H, Komada Y.
  • Journal Title: Pediatr Blood Cancer Volume: 61 Issue: 7 Pages: 1160-1161
  • DOI: 10.1002/pbc.24965
  • Peer Reviewed / Open Access
• [Presentation] Clinical outcome of newly diagnosed pediatric acute myeloid leukemia: Single institute experience (2014)
  • Author(s): 岩本彰太郎、岩佐正、木平健太郎、天野敬史郎、豊田秀実、出口隆生、平山雅浩、堀 浩樹、東 英一、駒田美弘
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-11-01