藉由一次臨床的追蹤研究,，科學(xué)家發(fā)現(xiàn)了白血病患病情惡化的分子線索,，而這個(gè)發(fā)現(xiàn)不但有助于對(duì)這種白血病的病情發(fā)展有所了解,，更有可能因此發(fā)展出治療的新方法。
急性骨髓性白血病 (AML)是骨髓中不正常的血球細(xì)胞,，不斷的異常分裂所造成,，目前除了以骨髓移殖的方式治療外，臨床上還可以選擇用化學(xué)藥物加以治療,，但統(tǒng)計(jì)資料顯現(xiàn)就僅僅 20%的病人具有效果,，因此深入的了解血癌細(xì)胞發(fā)病惡化的過程，一直是科學(xué)家的目標(biāo),。
由德州大學(xué)安德森研究中心 Steve Kornblau醫(yī)生所領(lǐng)導(dǎo)的研究團(tuán)隊(duì),，長期的追蹤分析188 位AML 病患的臨床檢體，并且配合了解病患的病情發(fā)展,，結(jié)果找到了3個(gè)分子標(biāo)靶,，參與的研究人員發(fā)現(xiàn)，如果病人的血癌細(xì)胞,，這 3個(gè)分子都屬于休眠的狀態(tài),，那么確定發(fā)病后的平均存活時(shí)間，大約為 78.6周,，若有 1個(gè)標(biāo)的分子活化了,，那平均存活時(shí)間降到57.9 周，而2 個(gè)分子同時(shí)在癌細(xì)胞里活化,，那么這種病患約有42.3周的存活時(shí)間,，最不幸的是血球細(xì)胞檢體里 同時(shí)測(cè)到了這 3個(gè)指標(biāo)分子的活動(dòng)，那么病患的生命可能只剩下23.4 周,。
研究人員將這一個(gè)突破性的發(fā)現(xiàn) 發(fā)表在最新一期血液(Blood) 期刊中并希望這樣的線索,，不僅僅是將來臨床診斷的工具，更有機(jī)會(huì)因此而發(fā)展出新的治療方法與治療藥物,。
原始出處：
Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia
Steven M. Kornblau, Matthew Womble, Yi Hua Qiu, C. Ellen Jackson, Wenjing Chen, Marina Konopleva, Elihu H. Estey, and Michael Andreeff
Blood 2006 108: 2358-2365. Prepublished online June 8, 2006; DOI 10.1182/blood-2006-02-003475 [Abstract] [Full Text] [PDF] [Supplemental Tables]
Full Text (PDF)
Deregulation of signal transduction pathways (STPs) may promote leukemogenesis by conferring cell proliferation and survival advantages in acute myelogenous leukemia (AML). Several agents targeting STPs are under development; however, redundancy and cross-talk between STPs could activate multiple downstream effectors and this could negate the effect of single-target inhibition. The frequency of concurrent activation of multiple STPs in AML and the prognostic relevance of STP activation in AML are unknown. STP protein expression (PKC, ERK2, pERK2, AKT, and pAKT) was measured by Western blot in samples from 188 patients with newly diagnosed, untreated AML. In univariate and multivariate analysis high levels of PKC, ERK, pERK, and pAKT, but not AKT, were adverse factors for survival as was the combination variable PKC-ERK2&pERK2-pAKT. Survival progressively decreased as the number of activated pathways increased. Patients were more likely to have none or all 3 pathways activated than was predicted based on the frequency of individual pathway activation, strongly suggesting that cross-activation occurred. Simultaneous activation of multiple STPs is common in AML and has a progressively worse adverse effect on prognosis. It is thus likely that only combinations of agents that target the multiply activated STPs will be beneficial for patients with AML.
Related Article in Blood Online:
Leukemia does not live by 1 lesion alone
Judith E. Karp
Blood 2006 108: 2133-2134. [Full Text]
