Analysis of the relationship of cytogenetic results with serum free light chain ratio κ/λ(FLC-r, Freelite^TM), heavy/light chain pairs of immunoglobulin ratio (HLC-r, Hevylite^TM), and selected prognostic factors assessed at diagnosis of multiple myeloma

Czech version

Authors: V. Ščudla ^1,2; J. Balcárková ²; P. Lochman ³; M. Mlynárčiková ²; T. Pika ²; J. Minařík ²; J. Zapletalová ⁴; M. Jarošová ²
Authors‘ workplace: 3. interní klinika-nefrologická, revmatologická a endokrinologická, Lékařská fakulta Univerzity Palackého a Fakultní nemocnice v Olomouci ¹; Hemato-onkologická klinika, Fakultní nemocnice a Lékařská fakulta Univerzity Palackého v Olomouci ²; Oddělení klinické biochemie, Fakultní nemocnice v Olomouci ³; Ústav lékařské biofyziky, Lékařská fakulta Univerzity Palackého v Olomouci ⁴
Published in: Transfuze Hematol. dnes,22, 2016, No. 2, p. 77-89.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

Introduction:
Assessment of serum levels of free light chains κ/λ(FLC-κ/λ) and recently of heavy/light chain immunoglobulin pairs (HLC) has extended the traditional algorithm of laboratory tests in multiple myeloma (MM). The aim of the study was to evaluate the relationship between standard prognostic MM factors, FLC-κ/λ ratio (^sFLC-r), modified „involved/uninvolved“ FLC ratio (^mFLC-r), the difference „involved – uninvolved“ FLC (FLC-dif), standard HLC-κ/λratio (^sHLC-r), modified „involved/uninvolved” HLC ratio (^mHLC-r), and the difference „involved-uninvolved“ HLC (HLC-dif) with the results of cytogenetic analysis at the time of MM diagnosis.

Patients and methods:
In a group of 97 patients with MM, we assessed serum levels of FLC using the FreeliteTM method and calculated the following indices: ^sFLC-r, ^mFLC-r and FLC- dif. Using the Hevylite^TM method, we assessed serum levels of HLC pairs and calculated the following indices: ^sHLC-r, ^mHLC-r and HLC-dif. For cytogenetic analysis of myeloma plasmocytes, we used fluorescent in situ hybridization with immunofluorescent staining of plasma cells (FICTION, “Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms“).

Results:
We confirmed a significant relationship between complex karyotype, del(13)(q14) and chromosome 1q21 gain with a decrease of Hb < 100 g/l; del(13)(q14) with thrombocytopenia < 150 x 10⁹/l and increased creatinine levels; and in the case of t(14;16)(q32;q23) also a relationship with ß₂-microglobulin (ß₂-M) > 5.5 mg/l; deletion del(17)(p13) (TP53) with increased ß2-M and trisomy of chromosomes 15 and 17 with MIg > 25 g/L. ^sFLC-r index levels were significantly elevated only in the case of del(13q14). However, after focusing on the group with ^sFLC-r < 0.01 and > 100, we found a significant relationship with del(13)(q14), del(17)(p13) and complex karyotype. The presence of 1q21 gain, del (17)(p13), complex karyotype and trisomy 17 had significantly higher levels of mFLC-r and in patients with cut off ³ 79.6 we found del(13)(q14), chromosome 1q21 gain and complex karyotype. In the cohort with FLC-dif ³ 185 there was an association with del(13)(q14), del(17)(p13) and complex karyotype. The relationship between ^sHLC-r and other assessed cytogenetic markers was insignificant except for the relationship with t(4;14)(p16;q32). One original contribution is the discovery of significantly increased ^mHLC-r levels in the case of 1q21 gain, complex karyotype and trisomy of chromosome 17 as well as t(4;14)(p16;q32) translocation. This finding was confirmed by the corresponding results of HLC-dif analysis in the group with ^mHLC-r ³31.6. Significantly higher serum MIg concentration was found only in the case of chromosome 15 trisomy.

Conclusion:
The study confirmed a statistically significant relationship between „high-risk“ structural changes, i.e. t(14;16)(q32;q23), del(13)(q14), del(17)(p13), 1q21 gain and complex karyotype with standard prognostic factors characterized by their relationship with the extent and biological features of MM. Our contribution towards a deeper understanding of MM pathobiology is the uncovered significant relationship between ^mFLC-r and del(13)(q14), 1q21 gain and del(17)(p13), as well as our original discovery of the significant relationship between ^mHLC-r and also partly HLC-dif. with prognostically unfavourable aberrations t(4;14)(p16;q32), chromosome 1q21 gain and complex karyotype.

Key words:
multiple myeloma – prognostic factors – free light chains of immunoglobulin – heavy/light chain pairs of immunoglobulin – fluorescent in situ hybridization

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