Influence of cytochrome P450 and glutathione S transferase polymorphisms on response to nilotinib therapy among chronic myeloidleukemia patients from Pakistan.

BACKGROUND: Cytochrome P450 (CYP) and glutathione S transferases (GSTs) are important biotransforming enzymes responsible for detoxification of anticancer drugs and carcinogens. Polymorphisms in these enzymes may greatly influence the susceptibility to CML and overall efficacy of tyrosine kinase inhibitors. This study was aimed to estimate the possible influence of the polymorphisms of GSTs and CYP in the occurrence of CML as well as in predicting therapeutic outcome of nilotinib therapy in Pakistani CML patients. METHODS: The polymorphic variability in CYP 1A1*2C, GSTP1 (A3131G), GSTT1 and GSTM1 was assessed either by RFLP or multiplex PCR. The BCR ABL1 transcripts were quantified by qPCR to monitor response to nilotinib. RESULTS: The CYP1A1*2C heterozygous and GSTP1 homozygous polymorphisms seemed to be a contributing factor in developing CML. Altogether, there were 12 non-responders, 66 responders and 21 partial responders. The most frequent genotype was null GSTM1 in responders followed by CYP 1A1 and GSTP1 -wild type (p = < 0.05). Whereas, homozygous GSTP1 and GSTT1 null genotype is significantly higher only among nilotinib non-responders. CONCLUSION: Hence, it can be concluded that wild type CYP1A1, GSTP1 and null GSTM1 may be frequently linked to favorable outcome in patients treated with nilotinib as depicted by sustained deep molecular response in most CML patients.

Possible correlation of electrochemiluminescence based numerical cut off index value with concentration of anti-SARS-CoV-2 antibody: Is it worth reporting?

Background: Many laboratories are reporting a numerical cutoff index value (COI) value for most anti-SARS-CoV-2 qualitative tests. These numerical values in patients' report ultimately created great confusion in the public and physicians, therefore this study was designed to evaluate the correlation of electrochemiluminescence (ECLIA) based numerical COI values with quantitative ELISA of anti-SARS-CoV-2 antibody. Design and Methods: Two hundred and twenty-eight (228) recovered COVID-19 patients were included; their serum samples were analyzed by quantitative ELISA and ECLIA for anti-SARSCOV- 2 antibodies. Results: One hundred and seventy-three (75.8%) patients tested positive by ECLIA and ELISA assay and thirty-seven (6.2%) were tested negative by both methods. A weak positive correlation (r=0.37) was found between numerical COI value of ECLIA with ELISA concentration, which was statistically significant with p<0.001. All values were dispersed on scatter plot and there was no significant linear relationship between ECLIA and ELISA assay. Conclusions: As both testing techniques are base upon the same immunological phenomena of detecting antibodies against nucleocapsid protein. We suggest that COI values are not meant to describe the immunity level of the individuals thus the physicians should not consider it as a quantitative value for antibody levels in COVID-19 patients.

NEUTROPHIL SCATTERING DATA DRIVEN PRE-MICROSCOPIC FLAGGING OF ACUTE LEUKEMIC CASES.

BACKGROUND: The hematology analyzer, Sysmex XN-1000, generates white blood cell count with varying scattering intensities during a complete blood count (CBC) analysis. OBJECTIVES: The objectives of the study were to study the predictive role of median and coefficient of variation of neutrophil scattering items in blood samples for differentiation of leukemic subjects. METHODS: We evaluated six neutrophil scattering parameters: neutrophil side scatter mean intensity, neutrophil side fluorescence light (SFL) mean intensity, neutrophil forward scatter mean intensity, neutrophil side scatter area distribution width (NE-WX), neutrophil SFL area distribution width (NE-WY), and neutrophil forward scatter area distribution width (NE-WZ), measured in white blood cell differential scattergram generated by the hematology analyzer (Sysmex XN-1000) at an academic medical center. RESULTS: We collected 433 blood samples from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) cases and normal controls. AML group showed highly significant differences in the mean values compared with the control group. Out of six neutrophil scattering items, NE-WX, NE-WY, and NE-WZ showed high efficiency, with area under the curve (AUC) values of 0.764, 0.748, and 0.757, respectively, to differentiate AML from ALL cases and control groups. When comparing combined acute leukemia cases (AML plus ALL) with the control group, NE-WX, NE-WY, and NE-WZ generated highly significant AUC values (0.840, 0.884, and 0.801, respectively). CONCLUSION: The neutrophil scattering parameters generated during CBC analysis provide a new tool for the prediction of acute leukemia and its lineage.

Neutrophil scattering data driven pre-microscopic flagging of acute leukemic cases

ABSTRACT Background: The hematology analyzer, Sysmex XN-1000, generates white blood cell count with varying scattering intensities during a complete blood count (CBC) analysis. Objectives: The objectives of the study were to study the predictive role of median and coefficient of variation of neutrophil scattering items in blood samples for differentiation of leukemic subjects. Methods: We evaluated six neutrophil scattering parameters: neutrophil side scatter mean intensity, neutrophil side fluorescence light (SFL) mean intensity, neutrophil forward scatter mean intensity, neutrophil side scatter area distribution width (NE-WX), neutrophil SFL area distribution width (NE-WY), and neutrophil forward scatter area distribution width (NE-WZ), measured in white blood cell differential scattergram generated by the hematology analyzer (Sysmex XN-1000) at an academic medical center. Results: We collected 433 blood samples from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) cases and normal controls. AML group showed highly significant differences in the mean values compared with the control group. Out of six neutrophil scattering items, NE-WX, NE-WY, and NE-WZ showed high efficiency, with area under the curve (AUC) values of 0.764, 0.748, and 0.757, respectively, to differentiate AML from ALL cases and control groups. When comparing combined acute leukemia cases (AML plus ALL) with the control group, NE-WX, NE-WY, and NE-WZ generated highly significant AUC values (0.840, 0.884, and 0.801, respectively). Conclusion: The neutrophil scattering parameters generated during CBC analysis provide a new tool for the prediction of acute leukemia and its lineage.