| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Research Abstract |
Acute megakaryoblastic leukemia (AMKL) has a diverse heterogeneity of the disease including morphology and cytogenetic studies. In children, 2 major subgroups have been described : AMKL developing in patients with Down syndrome (DS-AMKL) and AMKL in patients without Down syndrome (non-DS-AMKL). To compare the biological characteristics of blast cells with DS-AMKL and non-DS-AMKL, we compared the expression of hematopoietic transcription factors in blast cells derived from 19 children with AMKL (DS-AMKL : 11, non-DS-AMKL : 9). The morphology of blast cells was categorized into four groups : type 1, completely undifferentiated blasts ; type 2, intermediately differentiated blasts with cytoplasmic blebs ; type 3, blasts with dysmegakaryocytopoiesis ; type 4, blasts with deep blue cytoplasm. To define the differentiation stage by molecular level, we quantified the expression of transcription factors related to megakaryo-erythroid cell lineages ; GATA1, GATA2, FOG-1, NF-E2, SCL, PU.1, C/EBPα, c-mpl, Epo-R, CD41b, βglobin. In conclusion, blasts of DS-AMKL differentiated into not only megakaryocyte but also erythroid lineage because of overexpression of glycophorin A and βglobin under the GATA1 gene mutations. DS-AMKL should be classified into other categories apart from non-DS-AMKL considering the totally different patterns in gene alterations and levels of transcription factors.
|
