| Background: Multiple Myeloma (MM) is a kind of malignant plasmacell dyscrasia on B lymphocyte and malignant tumor of hematopoietic system.Currently, chemotherapy is a major treatment for that and multi-drugchemotherapy may use large dose glucocorticosteroid (GC) which mainlyworks. It is confirmed that GC may function by85%in VAD regimen. GCmay enter into the cancer cell via active diffusion, bind with cytoplasmic GCreceptor and transport into cell nucleus, and then combine with GC responseelements on DNA, functioning as transcription factor and startingtranscriptional activation, so to regulate downstream gene and induce celldeath. Wang Jialin et al. confirmed that myeloma cell strain KM3has moreGR than peripheral blood lymphocyte of normal human and found that the celldeath increased with the hormone concentration added in the cell strain KM3culture system. However, steroid resistance was frequently occurred on MMpatients during the treatment, which may impair the therapeutic effect andprognosis and even be life-threatening. Provided that timely detection of suchsteroid resistance on MM patients and replacing by other medicine areavailable, it may improve the treatment outcome and extend the survival time.FKBP51is an immunophilin and rich in lymphocytes. It is able to bind withthe acceptor site in GR complex via3TPR (tetratricopeptide repeat) loci atC-ternimus so to decline the binding between GR and GC and the transportability towards cell nucleus.Objective: This paper attempts to observe, on the basis of FKBP51index, the correlation between KFBP51and the curative effect ofchemotherapy containing large dose hormone on MM patients; to study theparticipation of FKBP51in the formation of steroid resistance; and to providethe basis for chemotherapy exerted on MM patients.Method: Collect40bone marrow biopsy samples with consent of MM patients hospitalized in our hospital from June2012to December2012. Viatissue fixation in10%neutral formalin solution, decalcification, paraffinembedding and slicing, the samples undergo HE staining to observe themorphological structures of both normal and diseased tissues; then undergoimmunohistochemical SP method to detect CD38and CD138. Providing bothare of positive expression, clearly mark the plasmocyte; on that basis, observethe expression of FKBP51on the plasmocyte. In the meantime, collect suchclinical data of the patients as Hb, Plt, serum creatinine, β2-microglobulin,plasmocyte proportion (%), blood calcium level, LDH, serum albumin andserum globulin, as well as the said indexes after2~3treatment courses byVTD or VAD regimens. Those40cases are divided into3groups, effectivegroup, refractory group，and the newly diagnosed group, to analyze theinfluence of positive rate of FKBP51on the treatment effect.Result:1Those40cases are divided into effective group, refractory group andthe newly diagnosed group, the positive rate of FKBP51is11.1%for effectivegroup,70%for refractory group and42.9%for the newly diagnosed group(ITG). By analyzing the positive expression among three groups, thedifference between effective group and refractory group has statisticalsignificance with P=0.033and P＜0.05; and that both between effective groupand the newly diagnosed group and between refractory group and the newlydiagnosed group has no statistical significance with P＞0.05n. In total,17cases have positive FKBP51expression and23negative, effective group has alower positive expression rate of FKBP51and better therapeutic effect. Thedifference both between effective group and the newly diagnosed group andbetween refractory group and the newly diagnosed group has no statisticalsignificance, however, from the clinical data we can conclude that the caseswith positive expression would have poor therapeutic effect and those withnegative expression would have better therapeutic effect.2The effective group consists of9cases,1having positive FKBP51expression and8negative. For the statistical analysis on clinical date beforeand after treatment, Hb、Plt、serum creatinine、β2-microglobulin、ratio ofplasma cells、calcium、LDH、serum albumin、serum globulin P＞0.05, thedifference has no statistical significance. However, its value is almost within normal range both before and after treatment, having no marked changes,which indicates that the patients are of stable condition and VAD and VTDchemotherapy does function.3The refractory group consists of10cases,7having positive FKBP51expression and3negative. For the statistical analysis on clinical date beforeand after treatment, Hb, plasmocyte proportion, serum globulin P＜0.05, thedifference has statistical significance that anemia aggravates and tumorburden and globulin proportion increases; serum creatinine, LDHmicroglobulin P＞0.05, the difference has no statistical significance, however,clinical date are higher than the normal values before and after treatment; Plt,blood calcium level, serum albumin P＞0.05, the difference has no statisticalsignificance, the3indexes are almost within normal range both before andafter treatment. After2~3courses of VTD or VAD treatment, these10patients’ condition has not been controlled and therefore both VTD and VADregimens failed.4The newly diagnosed group consists of21cases,9having positiveFKBP51expression and12negative. For the statistical analysis on clinicaldate of the9cases before and after treatment, plasmocyte proportion, serumalbumin, serum globulin P＜0.05, the difference has statistical significancethat bone marrow plasmacyte proportion increases after treatment,hypoproteinemia exacerbates and globulin proportion increases; Plt, bloodcalcium level＞0.05, the difference has no statistical significance and the said2indexes are almost within normal range both before and after treatment; Hb,serum creatinine, LDH, β2-microglobulin P＞0.05, the difference has nostatistical significance, after treatment, however, the above4indexes are allbeyond normal range; It follows that2~3courses of VTD or VAD treatmentis not satisfying.For the statistical analysis on clinical date of the12cases before and aftertreatment, Hb, β2-microglobulin, plasmocyte proportion, serum globulin P＜0.05, the difference has statistical significance that Hb returns to normal aftertreatment, β2-microglobulin drops to normal level, bone marrow plasmocyteproportion dramatically declines, marrow has partial even complete remissionand serum globulin also sharply declines; Plt, serum creatinine, blood calciumlevel, LDH, serum albumin P＞0.05, the difference has no statistical significance.2~3courses of VTD or VAD treatment indeed enables clinicaldate basically return to normal level, improving clinical symptoms and havinga better therapeutic effect.Conclusion:Effective Group and Refractory Group have different positive expressionrate of FKBP51and effective group has the lower with a better therapeuticeffect; it might be for fewer cases. Effective Group and The Newly DiagnosedGroup as well as Effective Group and The Newly Diagnosed Group haveundifferentiated positive expression rate of FKBP51; the cases with positiveexpression of FKBP51for Refractory Group and The Newly DiagnosedGroup have poor therapeutic effect and those with negative expression ofFKBP51for Effective Group and The Newly Diagnosed Group have bettertherapeutic effect. |
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