BCR-ABL Transcript Level as Compared to LDH and Uric Acid Among Chronic Myeloid Leukemic Patients

Recent Pat Anticancer Drug Discov. 2021;16(3):445-455. doi: 10.2174/1574892816666210222152126.

Abstract

Background: Chronic myeloid leukemia is characterized by the presence of the Philadelphia chromosome, which is caused by the breakpoint cluster region-Abelson fusion or joined gene. A high concentration of BCR-ABL transcripts level can strongly forecast cytogenetic and hematologic reversion in CML patients. However, the molecular test for BCR-ABL is costly and hardly available in developing countries with low and middle-income. Owing to this, it is required to examine other cost-effective and best diagnostic (prognostic) biomarkers.

Objective: The present study aimed to estimate the total LDH and uric acid level as compared to BCR-ABL transcript level among treated and treatment-naive Chronic Myeloid Leukemia (CML) patients.

Methods: A comparative cross-sectional study design was used to include eighty-one (81) CML patients tested for BCR-ABL by GeneXpert RT-PCR transcript level at Tikur Anbessa Specialized Hospital. The current study correlates LDH with BCR-ABL and hematological parameters using the spearman correlation, Mann-Whitney U test, and roc curve data analysis tool.

Results: A total of 81 CML patients were assayed; 46(56.8%) of them were in the medically treated group, and the remaining 35 (43.2%) were treatment-naive patients. Significant positive correlations were observed between LDH and BCR-ABL (r=0.79, P<0.001).The correlation coefficient value of uric acid (r=0.295, p<0.008) with BCR-ABL showed a weak correlation between the two test parameters. There was a statistically noteworthy (p<0.05) difference in the median level of BCR-ABL and LDH among patients in the treatment group (median=21%, 350 U/L) and the treatment- naive group (median=57%, 1246 U/L), respectively. For uric acid, there was no statistically significant (p<0.542) difference between the study group. The AUC for LDH, Basophil, and WBC was 0.881, 0.889, and 0.748, respectively, which showed better performance for the follow-up of patients with CML than uric acid (0.695) and platelets (0.70).

Conclusion: The CML LDH value strongly correlated with BCR-ABL transcript level, whereas uric acid was weakly correlated with BCR-ABL. Hence, in parallel with the BRC-ABL transcript level, these findings could be a patent for confirming the capability of LDH as an alternative cost-- effective diagnostic, prognostic biomarker, and a novel therapeutic target in CML disease.

Keywords: BCR-ABL; LDH; blood cancer; chronic myeloid leukemia; real-time polymerase chain reaction.; uric acid.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Developing Countries
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Health Services Accessibility
  • Humans
  • Hydroxyurea / therapeutic use
  • Imatinib Mesylate / therapeutic use
  • L-Lactate Dehydrogenase / blood*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Prognosis
  • Pyrimidines / therapeutic use
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Uric Acid / blood*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Pyrimidines
  • RNA, Messenger
  • Uric Acid
  • Imatinib Mesylate
  • L-Lactate Dehydrogenase
  • Fusion Proteins, bcr-abl
  • nilotinib
  • Hydroxyurea