The detection and clinical significance of microparticles derived from lymphocytes in patients with multiple myeloma

doi:10.11958/20231100

Abstract

Abstract:

Objective To investigate the expression and clinical significance of lymphocyte-derived microvesicles (LMP) in patients with multiple myeloma (MM). Methods A total of 65 newly diagnosed MM patients were used as the initial diagnosis group, and 30 health examination volunteers were selected as the control group. After 4 courses of chemotherapy, 8 patients in the initial diagnosis group died within 3 months, and the remaining 57 patients were included in the post chemotherapy group. Flow cytometry was used to detect the expression of LMP in peripheral blood of three groups, as well as the immune phenotype expression of peripheral blood lymphocyte subsets and bone marrow MM cells in the initial diagnosis group. Values of LMP between different therapeutic groups after chemotherapy were compared. The receiver operating characteristic (ROC) curve was used to determine the cutoff value for predicting death for each LMP. For the high (H) group with LMP ≥ cut-off value and the low (L) group with LMP<cut-off value, Kaplan Meier survival analysis was performed. Variables with a P value<0.05 in Kaplan Meier analysis were included into Cox regression analysis to analyze influencing factors of patient death. The differences in lymphocyte subpopulations and myeloma cell immunophenotypes were compared between different LMP groups. Results The proportions of LMP, CD3⁺LMP and CD3⁺CD8⁺LMP were lower in the initial diagnosis group than those in the control group, while the proportions of NKLMP and CD4⁺/CD8⁺LMP were higher than those in the control group (P<0.05). The proportion of CD3⁺CD8⁺LMP was higher in the post chemotherapy group than that in the initial diagnosis group, while the proportion of CD3⁺CD4⁺LMP and the ratio of CD4⁺/CD8⁺LMP were lower than those in the initial diagnosis group (P<0.05). The proportion of CD3⁺LMP and ratio of CD3⁺CD8⁺LMP were higher in the CR+VGPR group than those in the PR+MR+PD group (P<0.01), while the proportion of NKLMP and ratio of CD4⁺/CD8⁺LMP were lower than those in the PR+MR+PD group (P<0.05). Kaplan Meier analysis showed that the median survival time (OS) was shorter in the LLMP group than that of the HLMP group (P<0.01). The median OS was shorter in the LNKTLMP group than that in the HNKTLMP group (P<0.05). Cox regression analysis showed that LLMP and LNKTLMP were independent risk factors for patient mortality, with HR 4.620 and 2.706 (P<0.05). The proportions of CD3⁺CD4⁺T and CD4⁺/CD8⁺T were higher in the LLMP group than those in the HLMP group (P<0.05). The proportion of CD117⁺ in MM cells was higher in the LLMP group than that in the HLMP group (P<0.05). Conclusion Patients with MM have abnormal secretion of LMP. The LMP and NKTLMP are closely correlated with prognosis of MM. Targeted regulation of LMP secretion may improve the survival and prognosis of MM.

Key words: multiple myeloma, flow cytometry, prognosis, B-lymphocytes, T-lymphocytes, lymphocyte-derived

CLC Number:

R733.3

Figures/Tables 11

References 32

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组别	n	LMP/%	CD3⁺LMP/%	CD3⁺CD4⁺LMP/%	CD3⁺CD8⁺LMP/%
对照组	30	7.20（6.98，8.10）	76.90（72.20，79.13）	35.71（33.68，39.59）	25.39（22.62，32.18）
初诊组	65	1.22（0.49，2.56）	63.01（55.81，73.38）	36.28（27.91，39.51）	21.42（13.35，27.52）
Z		7.346^＊＊	4.864^＊＊	0.865	3.047^＊＊
组别	CD4⁺/CD8⁺LMP		NKLMP/%	NKTLMP/%	BLMP/%
对照组	1.28（1.23，1.56）		12.19（9.16，18.03）	8.42（7.16，10.22）	9.96（9.06，10.66）
初诊组	1.63（1.12，2.31）		21.32（15.18，28.67）	9.76（5.73，14.78）	6.35（3.52，11.78）
Z	2.042^＊		4.472^＊＊	1.173	1.934

组别	n	LMP/%	CD3⁺LMP/%	CD3⁺CD4⁺LMP/%	CD3⁺CD8⁺LMP/%
对照组	30	7.20（6.98，8.10）	76.90（72.20，79.13）	35.71（33.68，39.59）	25.39（22.62，32.18）
初诊组	65	1.22（0.49，2.56）	63.01（55.81，73.38）	36.28（27.91，39.51）	21.42（13.35，27.52）
Z		7.346^＊＊	4.864^＊＊	0.865	3.047^＊＊
组别	CD4⁺/CD8⁺LMP		NKLMP/%	NKTLMP/%	BLMP/%
对照组	1.28（1.23，1.56）		12.19（9.16，18.03）	8.42（7.16，10.22）	9.96（9.06，10.66）
初诊组	1.63（1.12，2.31）		21.32（15.18，28.67）	9.76（5.73，14.78）	6.35（3.52，11.78）
Z	2.042^＊		4.472^＊＊	1.173	1.934

组别	n	LMP/%	CD3⁺LMP/%	CD3⁺CD4⁺LMP/%	CD3⁺CD8⁺LMP/%
初诊组	65	1.22（0.49，2.56）	63.01（55.81，73.38）	36.28（27.91，39.51）	21.42（13.35，27.52）
化疗后组	57	1.10（0.28，2.86）	68.67（53.23，79.91）	30.56（23.20，34.25）	28.00（18.61，34.29）
Z		0.338	1.208	2.497^＊	2.540^＊
组别	CD4⁺/CD8⁺LM		NKLMP/%	NKTLMP/%	BLMP/%
初诊组	1.63（1.12，2.31）		21.32（15.18，28.67）	9.76（5.73，14.78）	6.35（3.52，11.78）
化疗后组	0.99（0.93，1.33）		16.75（10.52，28.85）	9.39（4.88，13.07）	11.13（3.32，18.60）
Z	3.677^＊＊		1.950	0.834	1.634

组别	n	LMP/%	CD3⁺LMP/%	CD3⁺CD4⁺LMP/%	CD3⁺CD8⁺LMP/%
初诊组	65	1.22（0.49，2.56）	63.01（55.81，73.38）	36.28（27.91，39.51）	21.42（13.35，27.52）
化疗后组	57	1.10（0.28，2.86）	68.67（53.23，79.91）	30.56（23.20，34.25）	28.00（18.61，34.29）
Z		0.338	1.208	2.497^＊	2.540^＊
组别	CD4⁺/CD8⁺LM		NKLMP/%	NKTLMP/%	BLMP/%
初诊组	1.63（1.12，2.31）		21.32（15.18，28.67）	9.76（5.73，14.78）	6.35（3.52，11.78）
化疗后组	0.99（0.93，1.33）		16.75（10.52，28.85）	9.39（4.88，13.07）	11.13（3.32，18.60）
Z	3.677^＊＊		1.950	0.834	1.634

组别	n	LMP/%	CD3⁺LMP/%	CD3⁺CD4⁺LMP/%	CD3⁺CD8⁺LMP/%
CR+VGPR组	31	1.25（0.31，3.77）	72.58（66.54，81.79）	31.89（26.58，35.53）	33.15（26.33，37.03）
PR+MR+PD组	26	0.93（0.08，1.85）	56.12（46.31，76.69）	27.38（21.71，32.11）	20.66（12.61，30.90）
Z		1.626	2.948^＊＊	1.738	3.020^＊＊
组别	CD4⁺/CD8⁺LMP		NKLMP/%	NKTLMP/%	BLMP/%
CR+VGPR组	0.97（0.92，1.02）		15.61（8.86，19.17）	9.84（5.96，13.08）	9.71（3.43，15.59）
PR+MR+PD组	1.23（0.96，1.51）		23.01（12.66，33.75）	7.44（4.42，12.71）	13.36（3.21，22.32）
Z	2.275^＊		2.243^＊	0.713	1.330