Cytogenetic Classification of Acute Lymphoblastic Leukemia(ALL) Karyon Genes involved Leukemia subtype Clinical prognosis Hyperdiploid >50 Early pre- B-or pre-B-ALL Favorable (12: 21)(p12: q 22) TEL, AMLI Early pre-B-or pre- B-ALL Favorable tl:19)g23:13)PBx,E2A Pre-B-ALL Good with intensified therapy 18.)24. c-MYC-b Mature B-ALL (ALL-L3) Favorable without central nervous system disease t19)9g23:133) MLL, ENI Early pre-B-or T-ALL Poor in patients <l yr; favorable in T-ALL 14:1)1g2123)AF4,ML Early pre-B-ALL Poor in patients <l or >10 yr of age (9: 22)(934: q l1) ABL, BCR Early pre- B-or pre-B-ALL Poor Near haploid <30 Early pre-B-ALL oor chromosomes iNcludes t(8:: 14)(q24: q32), t(2: 8)(p 12: g 24), and t 48: 22)(24: q1 1)where heavy, K, and immunoglobulin genes are involved on chromosomes 14, 2 and 22 respectively
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Cytogenetic Classifications of Acute Myeloid Leukemia Group CALGB(96) MRC(97,98,100) GAMLCG(101) SWOG (99) Favorable t(15;17) t(15: 17)with any abnormality t(15;17) t(15: 17) with any abnormality inv(16/(16;16/del(16)inv(16/t(16;16/del(16q) inv(16/(16;16) invl6/(16;16del(16q) with any other abnormality with any other abnormality t(8;21) t(8: 21) with any other abnormality t(8: 21) t(8: 21) without del(9q)or Intermediate Normal karyotype Normal karyotype Normal karyotype Normal karyotype +8,-Y,+6,der(12p) Other abnormalities +8, -Y, +6, der(12p) 1 1q23 abnormality del(9q) or del(7q) without other abnormality Complex karyotype (23 but <5 abnormalities) All abnormalities of unknown prognostic significance Unfavorable Other abnormalities -5/del(5q)-7 5/del(5q).-7/del(7q)-5/del(5q).-7/del(7q nv(3q), del(9q), 17p abnormality inv(3), 17p nv(3),17pabn,20q,+13, t(9;22) t(9;22) I 1g23 1 1q23 abnormality (8: 21)with del(9q) complex karyotype Complex karyotypes with Complex karyotype Complex karyotypes with ≥5 abnormalities 3 abnormalities Unknown All other clonal karyotypes with <3 chromosomal abnormalities Abbreviations: CALGB, Cancer and Leukemia Group B: MRC, Medical research Council; SWOG, Southwestern Oncology Group; GAMLCG German AML Cooperative Group
白血病染色体易位 ALL AML 30% AMLt电 t821) 12% MYc BCR-ABL 7q35TCRB P98-HQXA9 14011/TCRao MYC /29 CBFD-MYH11 t8;14)t(28)822) inv(18) 1% FUS-ERG 20% MLL-AF9 E2A-PBX1 TELAML1 1%t1621) t81) t(1: 19) E2A-HLF t12:21 PML-RARa DEK-CAN 图7v) MLL fusio t17:10)t:111:11+41 t15;17)t1:17 NPM-MLF1 t5:17) Bcel Pro-B cell 口 Promyelocytic口 Myelodysplastic, diverse myel Most of the fusion genes involved in AL translocations are transcription factors(TFs): abnormalities in lineage commitment and differentiation Look AT Science. 278: 1059
Look AT. Science, 278: 1059 白血病染色体易位 Most of the fusion genes involved in AL translocations are transcription factors (TFs): abnormalities in lineage commitment and differentiation
More study should be done 1. Molecular characterization of undetecta ble abnormalities on the cytogenetic level 2. Characterization of additional chromosomal or molecular genetic abnormalities e.g. t(11; 17 in the well defined favorable cytogenetic group may influence clinical outcome 3. Characterization of cooperating genetic abnormalities may affect treatment response in stepwise leukemogenesis
More study should be done 1. Molecular characterization of undetectable abnormalities on the cytogenetic level 2. Characterization of additional chromosomal or molecular genetic abnormalities [e.g. t(11;17)] in the welldefined favorable cytogenetic group may influence clinical outcome 3. Characterization of cooperating genetic abnormalities may affect treatment response in stepwise leukemogenesis
Hematopoiesis: a model of svstems biomedicine Common Myeloid c○ Common Lymphoid Progenitor(c Progenitor (CLP) cD33·,cD34+,cD38 Hematopoietic CD10*, CD38+, TaT Stem Cell(HSC) cD34+,cD38 EMP BFU-E BFU-meg GMP CFU-baso T-cell B-cell cD33+ CD34+ cD13+,cD33 CD34+ progenitor progenitor CD34+ cD34+ CD2+, CD4+ CD38+,cD34+ IL-3 CD5+, CD7+ cD24+,cD19+ GM-CSF lL·11 L-3 L-6 lL·10 L·1 Pre-Pre-B GM-CSF CFU-E CFU-meg CFU-M CFU-G CFU-Eos IL-4. SF CD36 CSF-1 G-CSF GM-CSF GM-CSF Pre-B IL-4. IL-5 GM-CSF L-6.L-11 B cell IL-6. TP CSF.t lL-8) ast ce L-4.L-5.lL6 RBC platelets Mono Important players: Hematopoietic stem cells, cytokines, microenvironment
Hematopoiesis: a model of systems biomedicine Common Myeloid Progenitor (CMP) Hematopoietic Stem Cell (HSC) Common Lymphoid Progenitor (CLP) GMP EMP Important players: Hematopoietic stem cells, cytokines, microenvironment