Differential Expression of LMNA/C and Insulin Receptor Transcript Variants in Peripheral Blood Mononuclear Cells of Leukemia Patients

Abstract

Background: Recent research has identified alternative transcript variants of LMNA/C (LMNA, LMNC, LMNAΔ10, and LMNAΔ50) and insulin receptors (INSRs) as potential biomarkers for various types of cancer. The objective of this study was to assess the expression of LMNA/C and INSR transcript variants in peripheral blood mononuclear cells (PBMCs) of leukemia patients to investigate their potential as diagnostic biomarkers. Methods: Quantitative TaqMan reverse transcriptase polymerase chain reaction (RT-qPCR) was utilized to quantify the mRNA levels of LMNA/C (LMNA, LMNC, LMNAΔ10, and LMNAΔ50) as well as INSR (IR-A and IR-B) variants in PBMCs obtained from healthy individuals (n = 32) and patients diagnosed with primary leukemias (acute myeloid leukemia (AML): n = 17; acute lymphoblastic leukemia (ALL): n = 8; chronic myeloid leukemia (CML): n = 5; and chronic lymphocytic leukemia (CLL): n = 15). Results: Only LMNA and LMNC transcripts were notably present in PBMCs. Both exhibited significantly decreased expression levels in leukemia patients compared to the healthy control group. Particularly, the LMNC:LMNA ratio was notably higher in AML patients. Interestingly, IR-B expression was not detectable in any of the PBMC samples, precluding the calculation of the IR-A:IR-B ratio as a diagnostic marker. Despite reduced expression across all types of leukemia, IR-A levels remained detectable, indicating its potential involvement in disease progression. Conclusions: This study highlights the distinct expression patterns of LMNA/C and INSR transcript variants in PBMCs of leukemia patients. The LMNC:LMNA ratio shows promise as a potential diagnostic indicator for AML, while further research is necessary to understand the role of IR-A in leukemia pathogenesis and its potential as a therapeutic target.

Keywords: LMNA/C transcript variants; insulin receptor transcript variants; leukemia; mononuclear cells.

Figure 1

TaqMan qRT-PCR measurement of relative mRNA expression levels of LMNA in (A) normal versus leukemic subjects and (B) following stratification into the four primary leukemias (AML, CML, ALL and CLL). The error bars represent mean ± S.E.M.; ** p < 0.001; * p < 0.05.

Figure 2

mRNA expression of LMNC in PBMCs of both normal and leukemic subjects. In the case of leukemia, the circulating PBMCs are linked to a decrease in the levels of LMNC mRNA expression (A). Furthermore, when stratified into the four primary leukemias (AML, CML, ALL, and CLL), reduced expression of LMNC is observed (B). The error bars in the figure represent the mean ± S.E.M., while the symbols ** and * indicate statistical significance with p-values < 0.001 and 0.05, respectively.

Figure 3

Comparison of the LMNC:LMNA mRNA ratio between normal and leukemic subjects in (A), and the LMNC:LMNA mRNA ratio in the same samples after stratification based on the four primary leukemias in (B). The error bars in the figure represent the mean ± S.E.M. Furthermore, the asterisk (*) indicates statistical significance with a p-value < 0.05.

Figure 4

Normalized mRNA expression levels of IR-A in PBMC of both normal and leukemic subjects (A). The data are further categorized into normal and the four primary leukemic types (AML, CML, ALL, CLL) (B). The error bars in the graph represent the mean ± Standard Error of the Mean (S.E.M.). The significance of the results is indicated by the symbols ** (p < 0.001) and * (p < 0.05).