Inflammatory cytokine levels in patients with philadelphia chromosome-negative myeloproliferative neoplasms

doi:10.3969/j.issn.1673-8640.2021.02.009

Abstract

Abstract:

Objective To investigate serum levels of inflammatory cytokines in patients with classical myeloproliferative neoplasms（MPN） [tumor necrosis factor-alpha（TNF-α）,interleukin-1 beta（IL-1β）,interleukin-2 receptor（IL-2R）,interleukin-6（IL-6）,interleukin-8（IL-8）,interleukin-10（IL-10）] and their clinical significance. Methods The serum levels of TNF-α,IL-1β,IL-2R,IL-6,IL-8 and IL-10 were detected by chemiluminescence immunoassay（CLIA）in 50 patients with Philadelphia chromosome-negative（Ph^-） newly diagnosed MPN [MPN group,including 16 cases of polycythemia vera（PV）,25 cases of essential thrombocytosis（ET） and 9 cases of primary myelofibrosis（PMF）] and 20 healthy volunteers（control group）. Sanger sequencing was used to detect JAK2 and MPL mutations,and CALR mutation was detected by real-time fluorescent polymerase chain reaction（PCR） in MPN patients. Results The serum levels of TNF-α,IL-2R,IL-6 and IL-8 in MPN group were significantly higher than those in control group（P<0.001）,while IL-10 level was on the contrary（P<0.001）. There was no significant difference in serum IL-1β level between the two groups（P>0.05）. IL-2R level in PMF group was higher than that in PV and ET groups（P<0.05）. Among the JAK2 V617F mutation-positive patients,IL-2R level in the PMF group was also significantly higher than that in the PV and ET groups（P<0.01）;the levels of TNF-α and IL-8 in the PMF group were higher than those in the ET group（P<0.05）;the level of IL-6 in the PMF group was higher than that of the PV group（P<0.05）. Interestingly,the level of TNF-α in MPN patients with marrow fibrosis（MF）-3 was higher than that in patients with MF-0（P<0.05） and its IL-2R level was higher than that of patients with MF-2（P<0.05）. Conclusion Inflammatory cytokines（TNF-α,IL-1β,IL-2R,IL-6,IL-8 and IL-10）are abnormally expressed in MPN patients,and there are differences in the expression among the three subtypes of MPN. Cytokine levels might become potential reference indicator for MPN diagnostic classification and follow-up.

Key words: Tumor necrosis factor-alpha, Interleukin-1 beta, Interleukin-2 receptor, Interleukin-6, Interleukin-8, Interleukin-10, Myeloproliferative neoplasms

CLC Number:

R446.1

CHEN Pu, MA Yangting, CHEN Nan, YU Zhenglin, CHENG Yunfeng, PAN Boshen, GUO Wei, WANG Beili. Inflammatory cytokine levels in patients with philadelphia chromosome-negative myeloproliferative neoplasms[J]. Laboratory Medicine, 2021, 36(2): 167-172.

Figures/Tables 4

References 17

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基因名称	引物序列（5'~3'）	引物大小/bp
JAK2 V617F	F：AGCAAGCTTTCTCACAAGCA	20
	R：CTGACACCTAGCTGTGATCCTG	22
JAK2 exon12	F：TTTGGAGCAATTCATACTTTC	21
	R：ACAAAATAATTCCAATGTCAC	21
MPL W515L/K	F：CCGAAGTCTGACCCTTTTTG	20
	R：ACAGAGCGAACCAAGAATGC	20

基因名称	引物序列（5'~3'）	引物大小/bp
JAK2 V617F	F：AGCAAGCTTTCTCACAAGCA	20
	R：CTGACACCTAGCTGTGATCCTG	22
JAK2 exon12	F：TTTGGAGCAATTCATACTTTC	21
	R：ACAAAATAATTCCAATGTCAC	21
MPL W515L/K	F：CCGAAGTCTGACCCTTTTTG	20
	R：ACAGAGCGAACCAAGAATGC	20

组别	例数	TNF-α/ （pg/mL）	IL-1β/ （pg/mL）	IL-2R/ （U/mL）	IL-6/ （pg/mL）	IL-8/ （pg/mL）	IL-10/ （pg/mL）
MPN组	50	16.6 （9.7~31.2）^**	3.3 （2.5~3.5）	533（432~856）^**	7.5（2.6~12.5）^**	8.0（5.9~13.4）^**	3.3（2.5~4.8）^**
PV组	16	18.8 （12.5~31.5）^*	2.8 （2.6~4.2）	494（383~514）^*#	4.8（4.0~7.9）^*	8.1（6.2~14.3）^*	3.7（3.2~4.6）^*
ET组	25	13.3 （8.9~22.5）^*	2.7 （2.5~3.3）	523（400~815）^*#	7.9（2.0~12.7）^*	7.5（5.0~10.5）^*	3.0（2.2~3.4）^*
PMF组	9	39.5 （18.0~64.6）^*	2.5 （2.4~3.1）	935（856~1906）^*	11.7（8.2~20.5）^*	18.4（7.7~22.1）^*	3.0（2.3~4.4）^*
正常对照组	20	4.0 （4.0~5.0）	3.1 （2.9~4.0）	265（201~297）	2.0（2.0~2.0）	5.0 （3.5~5.0）	7.6（5.0~15.5）

组别	例数	TNF-α/ （pg/mL）	IL-1β/ （pg/mL）	IL-2R/ （U/mL）	IL-6/ （pg/mL）	IL-8/ （pg/mL）	IL-10/ （pg/mL）
MPN组	50	16.6 （9.7~31.2）^**	3.3 （2.5~3.5）	533（432~856）^**	7.5（2.6~12.5）^**	8.0（5.9~13.4）^**	3.3（2.5~4.8）^**
PV组	16	18.8 （12.5~31.5）^*	2.8 （2.6~4.2）	494（383~514）^*#	4.8（4.0~7.9）^*	8.1（6.2~14.3）^*	3.7（3.2~4.6）^*
ET组	25	13.3 （8.9~22.5）^*	2.7 （2.5~3.3）	523（400~815）^*#	7.9（2.0~12.7）^*	7.5（5.0~10.5）^*	3.0（2.2~3.4）^*
PMF组	9	39.5 （18.0~64.6）^*	2.5 （2.4~3.1）	935（856~1906）^*	11.7（8.2~20.5）^*	18.4（7.7~22.1）^*	3.0（2.3~4.4）^*
正常对照组	20	4.0 （4.0~5.0）	3.1 （2.9~4.0）	265（201~297）	2.0（2.0~2.0）	5.0 （3.5~5.0）	7.6（5.0~15.5）

组别	例数	TNF-α/（pg/mL）	IL-1β/（pg/mL）	IL-2R/（U/mL）	IL-6/（pg/mL）	IL-8/（pg/mL）	IL-10/（pg/mL）
PV组	15	18.8（13.5~30.6）	2.7 （2.6~3.2）	494（413~510）^**	4.8 （3.0~7.3）^*	8.1（6.3~14.0）	3.7 （3.3~4.4）
ET组	17	13.3 （8.9~20.8）^*	2.7 （2.5~3.4）	523（402~805）^**	7.9（2.0~12.6）	7.5（5.2~10.4）^*	3.1 （2.6~5.0）
PMF组	6	39.5（19.3~55.7）	2.4 （2.4~2.8）	935（874~1470）	11.7（8.6~19.4）	18.4（7.8~21.2）	3.0 （2.3~4.4）