慢性髓性白血病培訓(xùn)課件

1、第52屆ASH會(huì)議慢性髓性白血病相關(guān)文獻(xiàn)AbstractsLate breaking AbstractsOral and Poster AbstractsChronic Myeloid Leukemia - Therapy Chronic Myeloid Leukemia - Biology and Pathophysiology Education ProgramCML 2010: Where Are We Now and Where Can We Go?第52屆ASH會(huì)議慢性髓性白血病相關(guān)文獻(xiàn)第一部分 CML治療-TKI伊馬替尼比較大劑量與標(biāo)準(zhǔn)劑量伊馬替尼治療的有效性及安全性 （the G

2、erman CML-Study IV）分析伊馬替尼治療的分子反應(yīng)程度與生存的關(guān)系評(píng)估伊馬替尼治療老年患者的療效及安全性評(píng)價(jià)伊馬替尼治療青少年患者的臨床療效尼洛替尼評(píng)估尼洛替尼治療的有效性和安全性（ENESTnd Trial）達(dá)沙替尼評(píng)價(jià)達(dá)沙替尼治療的有效性和安全性（DASISION Trial）比較達(dá)沙替尼和伊馬替尼治療的有效性和安全性 （The S0325 Intergroup Trial）分析BCR-ABL激酶區(qū)突變與治療反應(yīng)的關(guān)系Oral and Poster Abstracts Late-breaking Abstracts第一部分 CML治療-TKI伊馬替尼Oral and PoSe

3、ven-Year Follow-up Data on Sequential Prospective Trials of Imatinib 400mg Vs 800mg Daily Schedule for Front-Line Treatment of Chronic Myeloid Leukemia (CML)Naveen Pemmaraju, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3438目的-比較使用伊馬替尼800mg與400mg作為CML一線治療的長期臨床療效結(jié)果IM800mg（n=208）I

4、M400mg （n=73）P值中位隨訪時(shí)間mos（范圍）79 (3-107)110 (2-116)-累積CCyR率91%87%0.49累積MMR 率87%78%0.0612 個(gè)月CCyR90%66%0.001*18個(gè)月MMR82%68%0.04*7年EFS 86% 76%0.049*7年TFS-0.467年OS-0.27因毒性中止治療16 (8%) 6 (8%) -Seven-Year Follow-up Data on SSeven-Year Follow-up Data on Sequential Prospective Trials of Imatinib 400mg Vs 800mg

5、Daily Schedule for Front-Line Treatment of Chronic Myeloid Leukemia (CML)Naveen Pemmaraju, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3438結(jié)論-7年跟蹤調(diào)查顯示：與伊馬替尼400mg相比，伊馬替尼800mg 12 個(gè)月CCyR 、18個(gè)月MMR、7年P(guān)FS明顯改善,但OS無差異-大劑量伊馬替尼治療CML有一定益處Seven-Year Follow-up Data on SSuperior CMR-Rates wi

6、th Tolerability-Adapted Imatinib 800 Mg Vs. 400 Mg Vs. 400 Mg + IFN In CML: The Randomized German CML-Study IV Rdiger Hehlmann, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Optimizing Front-Line Therapy in CML 357目的-評(píng)價(jià)大劑量伊馬替尼治療初診Ph+ CML-CP患者的療效研究設(shè)計(jì)-完全分子學(xué)緩解CMR被定義為BCR-ABL/ABLIS 0.01%-1012例CML患

7、者入組（338例IM 800mg；324例IM 400mg；350例IM聯(lián)合干擾素）-IM 800mg組，平均每日伊馬替尼劑量628mg；IM 400mg組，平均每日伊馬替尼劑量400mgSuperior CMR-Rates with ToleraRdiger Hehlmann, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Optimizing Front-Line Therapy in CML 357結(jié)果-IM 800mg組12個(gè)月緩解率顯著提高12個(gè)月累積CCyR:IM 800mg組為63%；IM 400mg及聯(lián)合組為50%12

8、個(gè)月累積MMR:IM 800mg組為54.8%；IM 400mg組為30.8%; 聯(lián)合組為34.7% 36個(gè)月內(nèi)IM 800mg組均有較高的CMR，且比IM 400mg組更快獲得CMR初始治療時(shí)間 (月) 累積發(fā)病率MMR (%) CMR (%) IM400 n=306 IM800 n=328 IM400 +IFN n=336 IM400 n=306 IM800 n=328 IM400 +IFN n=336 6 8.6 18.1 8.4 3 3.7 2.4 12 30.8 54.8 34.7 7.5 19.8 12.4 18 50.3 68.4 54.1 21.2 33.4 23.6 24 6

9、3 76.0 62.8 30.7 43 30.0 36 79.3 81.6 70.7 45.5 56.8 40.5 Superior CMR-Rates with Tolerability-Adapted Imatinib 800 Mg Vs. 400 Mg Vs. 400 Mg + IFN In CML: The Randomized German CML-Study IV Rdiger Hehlmann, MD 結(jié)果-IM 80Superior CMR-Rates with Tolerability-Adapted Imatinib 800 Mg Vs. 400 Mg Vs. 400 Mg

10、 + IFN In CML: The Randomized German CML-Study IV Rdiger Hehlmann, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Optimizing Front-Line Therapy in CML 357結(jié)論-大劑量伊馬替尼治療耐受性良好-伊馬替尼800mg組比400mg組獲得更高CMR-伊馬替尼800mg組比400mg組有更多患者獲得穩(wěn)定CMR Superior CMR-Rates with ToleraMolecular Response 1% BCR-ABL IS at 1

11、2 Months Is Associated with Improved Overall and Progression-Free Survival: the Randomized German CML-Study IV Martin C. Mller, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Rethinking Therapy Targets and Prognostic Factors 669目的-評(píng)估分子反應(yīng)程度與生存的關(guān)系研究設(shè)計(jì)-848例CML患者入組-3個(gè)分子反應(yīng)組 (1% BCR-ABL/ABLIS) -12個(gè)月

12、PFS和OS結(jié)果-12個(gè)月時(shí)，341例患者獲得MMR(BCR-ABL/ABLIS1%-與BCR-ABL/ABLIS 1%組相比， BCR-ABL/ABLIS 0.1%-1%和MMR組3年P(guān)FS和OS更高M(jìn)olecular Response 1% BCR-ABLMartin C. Mller, MD Oral Session: Chronic Myeloid Leukemia - Therapy: Rethinking Therapy Targets and Prognostic Factors 669結(jié)論-更快、更深的分子反應(yīng)與PFS和OS的提高有關(guān)-關(guān)鍵臨界值似乎是1% BCR-ABL/AB

13、LIS水平（與CCyR密切相關(guān)）Molecular Response 65years): Results of the German CML-Study IVSusanne Saussele, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3411目的-評(píng)估伊馬替尼治療年齡大于65歲CML患者的療效及安全性研究設(shè)計(jì)-以65歲為年齡分界，分為IM 400mg和800mg組-觀測血液學(xué)、細(xì)胞遺傳學(xué)、分子學(xué)緩解時(shí)間，總生存率和不良反應(yīng)年齡65 (n=150）65years): Results of the Germ

14、an CML-Study IVSusanne Saussele, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3411結(jié)果有效性-年老與年輕患者間細(xì)胞遺傳學(xué)和分子學(xué)緩解率無顯著差異-IM 400mg組中，年老比年輕患者更慢獲得CCyR和MMR(CCvR: 14.2 月 vs 12.1 月,p=.019; MMR: 18.7 月 vs 17.5 月,p=.006）-IM 800mg組中，兩組間無差異 (CCvR : 7.7 月 vs 8.9 月, MMR: 9.9 月 vs 10.0 月)-3年總生存率兩組分

15、別為94.7% 和96.1% 安全性-血液學(xué)不良反應(yīng)：年老比年輕患者稍重-3、4級(jí)非血液學(xué)不良反應(yīng)：無差異Therapy with Imatinib In ElderTherapy with Imatinib In Elderly CML Patients (65years): Results of the German CML-Study IVSusanne Saussele, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster III 3411結(jié)論-年老患者使用伊馬替尼400mg和800mg均耐受性良好-應(yīng)用伊馬替尼8

16、00mg治療，年老與年輕患者獲得CCyR和MMR的中位時(shí)間無差異-應(yīng)用伊馬替尼400mg治療，年老患者比年輕患者更慢獲得CCyR和MMRTherapy with Imatinib In ElderAnalysis of Outcomes In Adolescents and Young Adults (AYA) with Chronic Myeloid Leukemia (CML) Treated with Upfront Tyrosine Kinase Inhibitors (TKI) Naveen Pemmaraju, MD Poster Session: Chronic Myeloid

17、Leukemia - Therapy: Poster 1234目的-評(píng)價(jià)酪氨酸激酶抑制劑治療青少年CML患者的臨床療效研究對(duì)象-年齡15至21歲的CML患者；移植患者排除結(jié)果年齡21 (n=422) P 值 總數(shù)Sokal 危險(xiǎn)度, n (%)低危 中危 高危 12 (92) 1 (8) 0 288 (68) 105 (25) 29 (7) 0.24 300 (69) 106 (24) 29 (7) CCyR, n (%) 7 (64) 384 (93) 0.008 391 / 425中位達(dá)CCyR時(shí)間 (月) 3 3 3 (2-64) MMR, n (%) 7 (64) 359 (87) 0

18、.0497 366 /424中位達(dá) MMR時(shí)間 (月) 9 6 6 (2-78) CMR, n (%) 1 (9) 160 (39) 0.06 161/424中位達(dá) CMR時(shí)間 (月) 1224 24 (3-84) 5年無事件生存79 90 0.26 5年無進(jìn)展生存 (%) 100 94 0.51 5年總生存 (%) 88 93 0.9 Analysis of Outcomes In AdolesAnalysis of Outcomes In Adolescents and Young Adults (AYA) with Chronic Myeloid Leukemia (CML) Treat

19、ed with Upfront Tyrosine Kinase Inhibitors (TKI) Naveen Pemmaraju, MD Poster Session: Chronic Myeloid Leukemia - Therapy: Poster 1234結(jié)論-與青少年CML患者相比，年長患者CCyR明顯提高；MMR和CMR也有升高趨勢-青少年與年長CML患者EFS，TFS和OS無差別Analysis of Outcomes In AdolesENESTnd Update: Continued Superiority of Nilotinib Versus Imatinib In P

20、atients with Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP) Timothy P. Hughes, MD, MBBS Oral Session: Chronic Myeloid Leukemia - Therapy: Optimizing Treatment Outcome207目的-評(píng)價(jià)尼洛替尼治療初診Ph+ CML-CP患者的療效和安全性(中位隨訪18個(gè)月的ENESTnd研究結(jié)果更新) 研究設(shè)計(jì)-隨機(jī)開放的多中心的3期臨床研究 -846例初診CML-CP患者入組-主要終點(diǎn)：12個(gè)月MMR (

21、0.1% BCR-ABLIS) -次要終點(diǎn)：24個(gè)月持續(xù)MMR-其他： 24 個(gè)月加速/急變率、EFS、PFS和OSENESTnd Update: Continued SupeTimothy P. Hughes, MD, MBBS Oral Session: Chronic Myeloid Leukemia - Therapy: Optimizing Treatment Outcome207 中位隨訪18個(gè)月的總體有效性Nilotinib 300 mg bid (n = 282) Nilotinib 400 mg bid (n = 281) Imatinib 400 mg qd (n = 28

22、3) MMR, % 66 P .0001* 62 P .0001* 40 Sokal危險(xiǎn)度, % 低危(n = 103, n = 103, n = 104) 70 69 51 中危 (n = 101, n = 100, n = 101) 67 63 39 高危 (n = 78, n = 78, n = 78) 59 51 28 BCR-ABLIS 0.0032% , % 21 P .0001* 17 P .0001* 6 CCyR, % 85 P .001* 82 P = .017* 74 向加速/急變進(jìn)展 不包括克隆演進(jìn), n (%) 2 (0.7) P = .006* 1 (0.4) P

23、= .003* 12 (4.2) 包括克隆演進(jìn), n (%) 2 (0.7) P 4log A Randomized Phase II Trial ofA Randomized Phase II Trial of Dasatinib 100 Mg Vs Imatinib 400 Mg In Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP): The S0325 Intergroup Trial 結(jié)果-達(dá)沙替尼組12個(gè)月分子反應(yīng)更深，BCRABL IS 中位下降3.3log；伊馬替尼組中位下降2.8log （P=

24、0.048）-兩組獲得HemCR和CCyR無顯著差異-死亡、復(fù)發(fā)及進(jìn)展均極少，OS和PFS相似-均無致命的不良反應(yīng)，達(dá)沙替尼最常見的3、4級(jí)血液學(xué)不良反應(yīng)是血小板減少IM 400mg (n=123) DAS (N=123) 2-sided P* HemCR 111 (90%) 104 (86%) 0.25 CCyR 40/58 (69%) 55/67 (82%) 0.097 3 log 39/90 (43%) 58/99 (59%) 0.042 4 log 18/90 (20%) 27/99 (27%) 0.31 4.5 log 13/90 (14%) 21/99 (21%) 0.26 12個(gè)

25、月OS 99% 100% 0.60 12個(gè)月PFS 96% 99% 0.19 A Randomized Phase II Trial ofA Randomized Phase II Trial of Dasatinib 100 Mg Vs Imatinib 400 Mg In Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP): The S0325 Intergroup TrialJerald P. Radich, MD Session: Late-Breaking Abstracts Session LBA-6

26、 結(jié)論 達(dá)沙替尼和伊馬替尼400mg治療初診Ph+ CML-CP均有效，且耐受性好與伊馬替尼相比，達(dá)沙替尼12個(gè)月時(shí)獲得更深的分子反應(yīng)達(dá)沙替尼和伊馬替尼OS和PFS相似達(dá)沙替尼有更多的3、4級(jí)血液學(xué)不良反應(yīng)A Randomized Phase II Trial ofPatients with Chronic Myeloid Leukemia In Chronic Phase Carrying More Than One BCR-ABL Kinase Domain Mutation Exhibit Poorer Response Rates and Outcomes to Second-Line

27、 Dasatinib Compared to Those with No or Only One BCR-ABL Mutation Alfonso Quints-Cardama Poster Session: Chronic Myeloid Leukemia - Therapy: Poster II 2297目的-分析CML-CP患者BCR-ABL激酶區(qū)突變與治療反應(yīng)的關(guān)系研究設(shè)計(jì)-回顧性分析-1150例對(duì)伊馬替尼耐藥或不耐受、使用達(dá)沙替尼治療的CML-CP患者入組-2期START-C (-013)、START-R (-017）、3期劑量優(yōu)化試驗(yàn)(-034) Patients with Chr

28、onic Myeloid Patients with Chronic Myeloid Leukemia In Chronic Phase Carrying More Than One BCR-ABL Kinase Domain Mutation Exhibit Poorer Response Rates and Outcomes to Second-Line Dasatinib Compared to Those with No or Only One BCR-ABL Mutation Alfonso Quints-Cardama Poster Session: Chronic Myeloid

29、 Leukemia - Therapy: Poster II 2297總數(shù) (N=1150) 24個(gè)月最佳反應(yīng)24個(gè)月無進(jìn)展生存12個(gè)月獲得的治療反應(yīng)與相應(yīng)的24個(gè)月無進(jìn)展生存24個(gè)月總生存MCyRa CCyRa 無基線突變, N=641 410/633 (64.8) 354/633 (55.9) 83.2% CCyR 96.5% 93.5 % PCyR 94.3% Other 75.1% 有基線突變, N=402 222/399 (55.6) 172/399 (43.1) 70.2% CCyR 93.4% 88.6% PCyR 86.6% Other 72.6% 一個(gè)基線突變, N=332

30、186/330 (56.4) 147/330 (44.6) 72.9% CCyR 92.3% 88.6% PCyR 88.1% Other 79.5% 大于一個(gè)基線突變, N=70 36/69 (52.2) 25/69 (36.2) 57.4% CCyR 100% 88.9% PCyR 75% Other 41.7% 結(jié)果Patients with Chronic Myeloid Patients with Chronic Myeloid Leukemia In Chronic Phase Carrying More Than One BCR-ABL Kinase Domain Mutatio

31、n Exhibit Poorer Response Rates and Outcomes to Second-Line Dasatinib Compared to Those with No or Only One BCR-ABL Mutation Alfonso Quints-Cardama Poster Session: Chronic Myeloid Leukemia - Therapy: Poster II 2297結(jié)論無論有、無BCR-ABL激酶區(qū)基線突變，達(dá)沙替尼療效顯著存在基線突變的CML-CP患者治療反應(yīng)率和PFS較低存在大于一個(gè)基線突變的CML-CP患者治療反應(yīng)率和PFS最低

32、Patients with Chronic Myeloid 第二部分：TKI耐藥的機(jī)制研究-相關(guān)信號(hào)通路JAK2信號(hào)STAT5信號(hào)Hedgehog信號(hào)通路NF-B信號(hào)Syk-Lyn-Axl信號(hào)通路Oral and Poster Abstracts 第二部分：TKI耐藥的機(jī)制研究-相關(guān)信號(hào)通路Oral anJAK2信號(hào)Jak2 Regulates Bcr-Abl In CD34+ Cells From Imatinib Mesylate-Resistant CML Patients-Bastianella Perazzona, Ph.D. JAK2-Mediated Extrinsic Surv

33、ival of CML Stem Cells: Exploring the Potential Combination of BCR-ABL and JAK2 Inhibitors In Vivo-Elie Traer, MD, PhD Combined Targeting of BCR-ABL and JAK2 with ABL and JAK2 Inhibitors Is Effective Against CML Patients Leukemic Stem/Progenitor Cells-Donna DeGeer, MSc Poster Session: Chronic Myeloi

34、d Leukemia - Biology and Pathophysiology, excluding Therapy: Poster I 1220 Oral Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: CML Stem Cell/Progenitor Biology 199 Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster I

35、I 3404JAK2信號(hào)Poster Session: Chronic JAK2信號(hào)JAK2抑制劑明顯降低BCR-ABL蛋白表達(dá)和磷酸酪氨酸177水平JAK2抑制劑有效誘導(dǎo)伊馬替尼耐藥的CD34+干、祖細(xì)胞死亡體內(nèi)同時(shí)抑制BCR-ABL和JAK2表達(dá)，顯著降低BCR-ABL表達(dá)的細(xì)胞數(shù)量,但骨髓毒性較大BCR-ABL和JAK2抑制劑聯(lián)用可有效殺傷TKI耐受的CML干、祖細(xì)胞Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster I 1220 Oral Se

36、ssion: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: CML Stem Cell/Progenitor Biology 199 Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster II 3404JAK2信號(hào)Poster Session: Chronic STAT5信號(hào)Distinct Functions of Stat5A and Stat5B

37、 in Chronic Myeloid Leukemia (CML): Stat5B Is Implicated in Survival and Self-Renewal and Stat5A in Imatinib Resistance-Ali G. Turhan, MD, PhD Bcr-Abl Directly Activates Stat5 Independent of Jak2-Oliver D. Hantschel, PhDHormone-Conditional Activation of Bcr-Abl Kinase Highlights Stat5 Anti-Apoptotic

38、 Pathway Prior to Promoting Cell Growth-Ratanakanit HarnprasopwatAdaptor Protein Lnk Negatively Regulates Bcr-Abl-Induced Cell Proliferation through Inhibition of the Stat5 Signaling Pathway-Takayuki Tabayashi, MDPoster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Thera

39、py: Poster I 1214Oral Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: NovelMolecular Mechanisms and Targets in CML 511Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster II 3380Poster Session: Chronic Myeloid Leukemia

40、- Biology and Pathophysiology, excluding Therapy: Poster II 3406STAT5信號(hào)Poster Session: ChronicSTAT5信號(hào)Stat5A在TKI耐藥的CML細(xì)胞中異常激活，抑制Stat5A可逆轉(zhuǎn)耐藥；Stat5B在CML細(xì)胞生存和自我更新中起重要作用Bcr-Abl不依賴JAK2信號(hào)直接激活Stat5Bcr-Abl/Stat5通路通過整合多種效應(yīng)分子(BCL-XL, HIF-1A, HSPA1A, WT1, PRAME)阻止細(xì)胞凋亡，成為治療Ph+白血病的潛在分子靶點(diǎn)銜接蛋白Lnk通過抑制Stat5信號(hào)轉(zhuǎn)導(dǎo)，負(fù)調(diào)控Bc

41、r-Abl誘導(dǎo)的細(xì)胞增殖，將為Ph+白血病的治療提供靶點(diǎn)Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster I 1214Oral Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: NovelMolecular Mechanisms and Targets in CML 511Poster Session: Chronic Myeloid

42、 Leukemia - Biology and Pathophysiology, excluding Therapy: Poster II 3380Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster II 3406STAT5信號(hào)Poster Session: ChronicHedgehog信號(hào)通路Hedgehog Signaling Is Useful as a Novel Molecular Marker for Predicting Relapse

43、 and Resistance During Chronic Myeloid Leukemia Treatment-Michele Cea Inhibition of Chronic Myeloid Leukemia Stem Cells by the Combination of the Hedgehog Pathway Inhibitor LDE225 with Nilotinib-Bin Zhang Human Blast Crisis Leukemia Stem Cell Inhibition with a Novel Smoothened Antagonist -Alice Shih

44、, BS Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster I 1215Oral Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Novel Molecular Mechanisms and Targets in CML 514Poster Session: Chronic Myeloid Leukemia - Biology an

45、d Pathophysiology, excluding Therapy: Poster I 1223Hedgehog信號(hào)通路Poster Session: ChHedgehog信號(hào)通路Hedgehog信號(hào)通路激活與BCR-ABL轉(zhuǎn)錄本升高直接正相關(guān)TKI耐藥的CML患者存在Hedgehog信號(hào)通路異常激活，可預(yù)測復(fù)發(fā)和耐藥阻斷Hedgehog信號(hào)可抑制TKI耐藥的CML細(xì)胞增殖Hedgehog抑制劑（LDE225）靶向白血病干細(xì)胞，與尼洛替尼聯(lián)用可有效清除TKI治療殘留的白血病干細(xì)胞Hedgehog抑制劑（SMO拮抗劑）與達(dá)沙替尼聯(lián)用抑制伊馬替尼耐藥的急變白血病干細(xì)胞自我更新Poster S

46、ession: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster I 1215Oral Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Novel Molecular Mechanisms and Targets in CML 514Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysio

47、logy, excluding Therapy: Poster I 1223Hedgehog信號(hào)通路Poster Session: Ch其他信號(hào)通路NF-BDistinct Roles for the NF-B Pathway In Myeloid and Lymphoid Transformation and Leukemogenesis by BCR-ABL-Mo-Ying Hsieh, BS Syk-Lyn-AxlQuantitative Phosphoproteomics Identified a New Syk-Lyn-Axl Signalling Pathway Involved

48、In Resistance to Nilotinib In Chronic Myeloid Leukemia Cells-Romain Gioia, Ph, D Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster I 1225Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster II 3376其他信號(hào)通路Post

49、er Session: Chronic 其他信號(hào)通路NF-B在BCR-ABL表達(dá)的白血病細(xì)胞中，NF-B部分通過經(jīng)典的IKK途徑被激活NF-B信號(hào)在BCR-ABL表達(dá)的髓系及淋系白血病發(fā)病機(jī)制中扮演不同角色NF-B信號(hào)在產(chǎn)生和/或維持CML干細(xì)胞中發(fā)揮作用， IKKs將成為治療Ph+白血病的新分子靶點(diǎn)Syk-Lyn-Axl定量磷酸蛋白質(zhì)組學(xué)發(fā)現(xiàn)了一個(gè)新的Syk-Lyn-Axl信號(hào)通路其在尼洛替尼耐藥中起重要作用Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Po

50、ster I 1225Poster Session: Chronic Myeloid Leukemia - Biology and Pathophysiology, excluding Therapy: Poster II 3376其他信號(hào)通路Poster Session: Chronic Education Program探討慢性期CML酪氨酸激酶抑制劑的優(yōu)化治療對(duì)于需要二線治療的患者，我們應(yīng)該做什么在2010年，CML還有哪些待解決的問題第三部分 繼續(xù)醫(yī)學(xué)教育CML 2010: Where Are We Now and Where Can We Go？Education Program第三部分 繼續(xù)醫(yī)學(xué)教育伊馬替尼（400mg/d）是初診CML慢性期患者的標(biāo)準(zhǔn)治療IRIS 8年隨訪結(jié)果EFS、無加速/急變生存率分別是82%、92%TKI治療大大降低CML死亡率部分患者仍存在耐藥和疾病進(jìn)展第二代TKI治療伊馬替尼耐藥的CML-CP患者，僅50%獲CCyR，加速期患者獲得CCyR率更低CML治療現(xiàn)狀CML治療現(xiàn)狀TKI治療CCyR比較