Comprehensive analysis of the RSK gene family in acute myeloid leukemia determines a prognostic signature for the prediction of clinical prognosis and treatment responses

The prognosis of acute myeloid leukemia (AML) remains poor although the basic and translational research has been highly productive in understanding the genetics and pathopoiesis of AML and a plethora of targeted therapies have been developed. Consequently, it is crucial to deepen the knowledge of molecular pathogenesis underlying AML for the advancement of new treatment options. A RSK gene family-related signature was constructed to investigate whether RSK gene family members were useful in predicting the prognosis of AML patients. The relationship between the RSK gene family-related signature and the infiltration of immune cells was further assessed using the CIBERSORT algorithm. The ‘oncoPredict’ package was used to analyze relationships between the RSK gene family-related signature and the sensitivity to drugs or small molecules. Patients were classified into two groups using the RSK gene family-related signature following the median risk score. Overall survival (OS) was significantly longer in patients with low-risk scores than that in patients with high-risk scores as showed by both training and validation datasets. Moreover, the signature was helpful in predicting 1-year, 3-year, and 5-year OS in training and validation datasets. In addition, it was identified that low-risk patients exhibited greater sensitivity to 20 drugs or small molecules and that high-risk patients had higher sensitivity to 38 drugs or small molecules. RSK gene family members, particularly RPS6KA1 and RPS6KA4, may help to predict prognosis for AML patients. Furthermore, RPS6KA1 may serve as a novel drug target for AML.</p

Segregation ratio analysis of the four F₂ populations.

<p>Segregation ratio analysis of the four F₂ populations.</p

Heading date variation and significance analyses of 28 CASLs and <i>Triticum aestivum</i> var. Chinese Spring (CS).

<p>Heading date variation and significance analyses of 28 CASLs and <i>Triticum aestivum</i> var. Chinese Spring (CS).</p

QTL locations, related maximum LOD values and their explanation of phenotypic variation for heading date detected in the four mapping populations.

<p>QTL locations, related maximum LOD values and their explanation of phenotypic variation for heading date detected in the four mapping populations.</p

Distribution of heading dates in four wheat F₂ populations.

<p>M: Middle value; CS: Chinese Spring; 2BS: CASL2BS; 3AL: CASL3AL; E1:CASL2BS×CS (Planting time: 11/10/2012); E2: CASL2BS×CS (Plant time:1/26/2013); E3: CASL3AL×CASL 2BS (Planting time: 11/10/2012); E4:CASL3AL×CASL 2BS (Planting time: 1/26/2013).</p

TaqMan^® estimation of <i>Ppd-B1</i> copy number in Chinese Spring (CS), TDIC140 and CASL2BS.

<p>Solid circles are genotypes known to have a photoperiod sensitive (<i>Ppd-B1b</i>) allele and open circles are genotypes known to have a day neutral (<i>Ppd-B1a</i>) allele. Copy number was estimated based on the <i>Ppd-B1</i>/Internal Positive Control (IPC) signal ratio. Means and standard deviations of three measurements are shown. T-tests show the classes that differed significantly from one another (*<i>p</i><0.001).</p

General heading date statistics for the four F₂ populations and their two parents.

<p>General heading date statistics for the four F₂ populations and their two parents.</p

Identification of the <i>Ppd-B1</i> gene on chromosome arm 2BS by SSCP analysis of 28 CASLs (#1-#28) and their parents.

<p>C: CS; and T: TDIC140. The black arrow indicates the TDIC band in CASL2BS (#17).</p