Expression and Prognostic Impact of Candidate Suppressor Sequence-Specific Single-Stranded DNA Binding Protein (SSBP2) in AML Using Reverse Phase Proteins Arrays (RPPA).

生物 分子生物学 川地34 染色体 癌症研究 细胞遗传学 染色体异常 基因 遗传学 核型 干细胞
作者
Steven M. Kornblau,Yihua Qiu,Wenjing Chen,Hong Liang,Farhad Ravandi,Kevin R. Coombes,Lalitha Nagarajan
出处
期刊:Blood [Elsevier BV]
卷期号:110 (11): 2394-2394
标识
DOI:10.1182/blood.v110.11.2394.2394
摘要

Abstract Sequence-specific single-stranded DNA binding protein 2 (SSBP2) is a candidate tumor suppressor gene, located at chromosome 5q13.3, that is thought to regulate hematopoietic growth and differentiation. Loss of SSPB2 expression is associated with deletions of chromosome 5 and replacement in cell lines induces partial differentiation and loss of clonogencity. Using a highly specific antibody, we studied the level of expression and prognostic relevance of SSBP2 protein expression (along with 51 other total and phospho proteins as described in ASH abstract #107, 2006) in leukemia-enriched samples from 423 patients (258 newly diagnosed, 47 primary refractory, 118 relapse 1, 2 or refractory) using high-throughput reverse phase protein array technology (RPPA). Levels of SSBP2 were lower, equal and higher than that of normal CD34+ cells in 2.7%, 58.7% and 11.6% of cases respectively. All 7 cases with low levels were female and 21/30 with high levels were male. The expression of SSBP2 was not equally distributed in the different FAB subtypes with the lowest median levels in M5 and the highest in M0, M1 and M2. Levels were significantly higher in favorable cytogenetics (t(8;21) and Inv (16) compared to intermediate (p=0.05) or unfavorable (p=0.008) cytogenetics. Median levels were lowest in cases with cytogenetic abnormalities on chromosome 5 or with an 11q23 abnormality. Levels were significantly higher in primary refractory and relapse samples compared to diagnostic samples. The levels of SSBP2 expression was strongly positively correlated with expression levels of anti-apoptotic proteins BCL2, Bcl-XL, caspase inhibitors SMAC, Survivin and XIAP, and inversely correlated with inactivated Bad-p112. Expression also was positively correlated with proliferation regulating proteins β-Catenin, Cyclin D, GSK3, Myc, P27, as well as VEGF receptor neuropilin and P53. Levels were strongly negatively correlated with activated signal transduction proteins (STP) including phosphorylated AKT (phosphorylated on threonine 308 or serine 473), pMEK, pERK2, pP38, pPKCα and as well as activated P70S6K. For outcome analysis martingale residuals were utilized to define an optimal cutpoint for dichotomization into groups with higher (n=130, 111 treated) vs. lower (n=128, 106 treated) SSBP2. Complete remission rates (58% vs. 63%, p=0.39), relapse rates (53% vs. 49%, P=0.59, and median remission duration (37 vs. 39 weeks, p=0.37) did not differ between patients with lower vs. higher SSBP2. However patients with higher SSPB2 levels had significantly longer median survival (40 vs. 31 weeks, p=0.015) compared to patients with lower SSBP2 levels. In summary, SSBP2 expression is heterogeneous in AML ranging from low in the poor and mixed prognosis subsets and high in the good prognosis t(8;21). Consistent with its demonstrated role in hematopoietic differentiation, the levels correlate negatively with expression of proliferation enhancing and STP. Nonetheless, the significance of positive correlation with antiapoptotic proteins is unclear at present. But the association with favorable longer overall survival suggests that therapeutic agents targeting the SSBP2 pathway function might have efficacy in AML.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
乌兰巴托没有海完成签到,获得积分10
刚刚
3秒前
lin关注了科研通微信公众号
4秒前
5秒前
兴奋小丸子完成签到,获得积分10
6秒前
7秒前
8秒前
8秒前
keyanxiaobai完成签到,获得积分10
9秒前
二十二点36完成签到,获得积分10
9秒前
量子星尘发布了新的文献求助10
10秒前
英勇星月完成签到 ,获得积分10
13秒前
zgt01发布了新的文献求助10
13秒前
新德里梅塔洛1号完成签到,获得积分20
16秒前
19秒前
wp完成签到,获得积分10
24秒前
splemeth完成签到,获得积分10
24秒前
雪白的紫翠完成签到 ,获得积分10
25秒前
哈哈完成签到,获得积分10
26秒前
淡定访琴完成签到,获得积分10
28秒前
大力云朵完成签到,获得积分10
30秒前
ADcal完成签到 ,获得积分10
30秒前
30秒前
tony完成签到,获得积分10
30秒前
苏苏完成签到,获得积分10
32秒前
WuFen完成签到 ,获得积分10
33秒前
淘宝叮咚完成签到,获得积分10
33秒前
高高从云完成签到 ,获得积分10
34秒前
情怀应助唐唐采纳,获得10
35秒前
科研肥料完成签到,获得积分10
36秒前
每天都在找完成签到,获得积分10
36秒前
桐桐应助zzw采纳,获得20
36秒前
36秒前
吕布完成签到,获得积分10
37秒前
37秒前
ChenYifei完成签到,获得积分10
41秒前
qq发布了新的文献求助10
41秒前
Smiley完成签到 ,获得积分10
44秒前
hzauhzau完成签到 ,获得积分10
44秒前
白桃完成签到 ,获得积分10
46秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038184
求助须知:如何正确求助?哪些是违规求助? 3575908
关于积分的说明 11373872
捐赠科研通 3305715
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022