白血病遗传学基础 白血病基因组解剖学计划(LGAP) Genes re-sequenced TFs: AML-1, CBFB, C/EBPa, GATA1,.yB GATA1p, GATA2, GATA2p, GATA3, MYE PU.1, Signaling molecule: PDGFRa, PDGFRB, c KIT/SCFR FLK2/FLT3 NRAS KRAS/CSBP NOTCH1 NOTCH2 NOTCH3
Genes re-sequenced: TFs: AML-1, CBFβ, C/EBPα, GATA1 , GATA1p , GATA2 , GATA2p , GATA3 , MYB , PU.1, … Signaling molecule: PDGFRa, PDGFRb, cKIT/SCFR, FLK2/FLT3, NRAS, KRAS, ICSBP, NOTCH1, NOTCH2, NOTCH3, … 白血病遗传学基础： 白血病基因组解剖学计划 (LGAP)
白血病遗传学基础 白血病基因组解剖学计划(LGAP) Class丨 mutations Class‖ mutations Confer proliferative and/or Serve primarily to impair survival advantage but do not hematopoietic differentiation affect differentiation and subsequent apoptosis BCR/ABL TEU/PDGFBR AML1/ETO. CBFB/SMMHC -N-RAS and K-RAS mutants and PMU/RARo fusions FLT3 activating mutations Point mutations in AML1 C/EBPa CML-like AML MDS-like TWO-hits hypothesis
白血病遗传学基础： 白血病基因组解剖学计划 (LGAP) Two-hits hypothesis
Acute Myeloid leukemia with recurrent genetic abnormalities in classification of WHo AML with t(8; 21: AML1-ETO AML with abnormal marrow eosinophilia and inv (16)or t(16, 16); CBFB-MYH11
Acute Myeloid leukemia with recurrent genetic abnormalities in classification of WHO • AML with t(8;21);AML1-ETO • AML with abnormal marrow eosinophilia and inv(16) or t(16;16);CBFb-MYH11
t(12;21) TEL-AML1 t(8;21) 30%of B-progenitor AML1-ETO t(3;2 c15% of AML AML1-EVI1 pediatric ALL Rare cases of inv (16) CML and MDS CBFB-SMMHC 415% of AML AML1 CBFB runt nomology domain Target genes TGTGGT MPO,儿3, GM-CSF CSF-1R
TEL基因相关的白血病 Chromosomal isease Translocation Fusion genes AML t(1;12)(q21;p13)TEL-ARNT AML t(1; 12 )(q25; p13) TEL-ABL2 AML, MDS t(3;12)(q26; q 22)TEL-MDSI-EVIl PTCL peripheral T-cell lymphoma) t(4;12)(p16;p13)|TEL-FGFR3 AML I t(4: 12)(q11;p13)BTL-teL CML t(5;12)(q31;pl3)|TEL-ACS2 AML, MDS t(5; 12)(33; p13)TEL-PDGFR B ALL t(6; 1 2 )(q23; p13)TEL-StL ALL CML t(9;12)(p24p13)| TEL-JAK2 MDS t(9; 12)(q22; p13) TEL-SYK ALL. CMLAUL t(9:12)(g34:; p13) TEL-ABL AMLALL t(12;13p13:q12)TEL-CDX2 AML t(12;15)(p13;925) TEL-NTRK3 AML t(12;21)(p13:9g2)| TEL-AMLI AML t(12: 22)(p13; q11)MNI-TEL
TEL 基因相关的白血病 Disease Chromosomal Translocation Fusion genes AML t(1;12)(q21;p13) TEL-ARNT AML t(1;12)(q25;p13) TEL -ABL2 AML,MDS t(3;12)(q26;q22) TEL -MDS1-EVI1 PTCL (peripheral T-cell lymphoma) t(4;12)(p16;p13) TEL -FGFR3 AML t(4;12)(q11;p13) BTL-TEL CML t(5;12)(q31;p13) TEL -ACS2 AML,MDS t(5;12)(q33;p13) TEL-PDGFRβ ALL t(6;12)(q23;p13) TEL -STL ALL,CML t(9;12)(p24;p13) TEL-JAK2 MDS t(9;12)(q22;p13) TEL-SYK ALL,CML,AUL t(9;12)(q34;p13) TEL-ABL AML,ALL t(12;13)(p13;q12) TEL -CDX2 AML t(12;15)(p13;q25) TEL -NTRK3 AML t(12;21)(p13;q22) TEL-AML1 AML t(12;22)(p13;q11) MN1-TEL