The Role of Immune Check Point Gene Expression of Pd-1 and Tim-3 in Patients with Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a hematopoietic cell cancer that spreads quickly to the blood and rapidly developing in the bone marrow. The prognosis for patients with acute myeloid leukemia (AML) is still poor, despite recent improvements in the therapeutic landscape. In hematological malignancies, immune checkpoint inhibitors have been studied, such as AML; however, the role of program cell death -1(PD-1) and T-cell immunoglobulin and mucin domain 3 (TIM3) in AML has not been thoroughly elucidated yet. Thus, the current study conducted to investigate the PD-1 and TIM‑3 gene expression in the AML patients and determine its associations with clinical outcomes and prognostic variables. The study collected 80 blood samples from acute myeloid leukemia (AML) patients and 40 blood samples from volunteer healthy individual were evaluated as control and real time quantitative (qRT-PCR) analysis was detect to performed PD-1 and TIM‑3 expression. The result showed there was non-significant (P>0.0001) in expression of TIM-3 in patients with AML, while expression of PD-1 statistically has high significant difference (P ≤ 0.0001). A cutoff value of PD-1 for patients vs. control was (0.853) with high sensitivity than cutoff value of TIM-3 for patients vs. control that can be diagnostically significant in distinguishing between patients and controls. Our data result showed that high expression of PD-1 in T cell is extremely correlated with progression of disease and down regulated gene expression of TIM-3 in AML patients

The role of miRNA -150 between different BCR-ABL p210 transcript levels and between different levels of imatinib optimal response in CML patients

The dysregulation of miRNA expression patterns is one of the many effects developments of cancer, miRNA has been found to express abnormally in hematological neoplasia such as chronic myeloid leukemia and solid malignancies. Resistance and the degree of response following tyrosine kinase inhibitor treatment are correlated with miRNA expression. Hence, in this study we tried to study the relationship of miRNA-150 between different breakpoint cluster region–Abelson (BCR- ABL) P210 transcript levels and the role miRNA- 150 between different levels of imatinib optimal response in chronic myeloid leukemia (CML). Our study included sixty chronic myeloid leukemia (CML) patients they were divided into two groups based on response to imatinib therapy, thirty samples of the optimal molecular response of chronic myeloid leukemia (CML) patients, and thirty samples of failure molecular response chronic myeloid leukemia (CML) patients. Thirty samples of apparently healthy volunteers were included and evaluated as control. According to the P210 BCR-ABL%, the results showed a significant difference (P= < 0.0001) between the responder and the failure response CML patients. Assessed the result of miRNA-150 showed a significant difference between both CML patients (P = < 0.0001), assessed miRNA-150 level among different response groups, and failure response of CML patients (P = 0.0002). A cutoff value of response vs. failure response (1.784) with high sensitivity can be a diagnostic value to differentiate between response and failure response. Changing gene expression with different amounts of miRNAs had an impact on drug-gene interactions, with consequences for cell growth and death. Gene expression of different levels miRNA-150 among of CML patients of imatinib therapy showed high expression in response patients than failure response patients. The gene expression level of miRNA-150 differs through different responses in CML patients

Serum Calcium And Phosphateleveelsin Patients With Chronic Myeloid Leukemia Taking Different Dose of Tyrosine Kinase Inhibitors

Objective: chronic myeloid leukemia (CML) is a myeloproliferative confusion characterized by the occurrence of an acquired mutation which affect the hematopoietic stem cell, treatment of CML with tyrosine kinase inhibitors (TKI) has resulted in high response rates compared to the interferon alpha and hydroxy urea. However, the long-term consequences of TKI had an effect on calcium (Ca++ ) and phosphate(PO4-2 ) levels which may have adverse events on the cardiac and skeletomuscular contraction. Methods:  in a cross-sectional study, 95 patients with CML receiving different TKI treatment for at least one year duration were randomly divided in to three groups: group (1) who received imatinib myselate (Gleevec) 400mgper oral per day,the second group were patients received gleevec 600mg-800mg/day, while the third group patients were received nilotinib 800mg/day as a second line therapy after failure to imatinib mylselate response . Results: in the present study,serum Ca++  level was a significant lower statistical different with p < 0.05 when compared with serum level of PO4-2inpatients treated with imatinib and nilotinib with lower serumCa++ and PO4-2levelsin imatinibpatientsgroup than patientsused nilotinib group with p-value 0.049 and 0.005 subsequently. Conclusion:  imatinib therapy with the long term use may cause hypocalcemia and hypophospatemia without significant correlation more than treatment with nilotinib where  significant correlation was between serum Ca++ and PO4-2and these changes may give an idea that disturbance of serum Ca++, PO4-2was multifactoria

Evaluation of the Safety of Imatinib Mesylate in 200 Iraqi Patients with Chronic Myeloid Leukemia in the Chronic Phase: Single-Center Study

OBJECTIVE: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML). During therapy, a few patients may develop hematological and non-hematological adverse effects. METHODS: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. RESULTS: Two hundred CML patients in chronic phase were included in this study; the male: female ratio was 0.7: 1 with mean age 39.06±13.21 years (ranged from 15-81 years). The study showed that the commonest hematological side effects were grade 2 anemia (12.5%) followed by leukopenia (8%) and thrombocytopenia (4%), while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%), followed by musculoskeletal pain (35.5%), then gastro-intestinal symptoms (vomiting, diarrhea) (19%). Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. CONCLUSION: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively

Assessment of Serum Ferritin, Serum Calcium, and Vitamin D Status in β-thalassemia Major Children and Adolescents in Al Rusafa Side in Baghdad

&lt;p&gt;ABSTRACT&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Beta Thalassemia is a genetic disorder inherited by autosomal recessive and occurs throughout the world, including Iraq. Patients with beta-thalassemia require blood transfusions for life, and this can lead to the accumulation of iron in the skin, kidneys, and liver, resulting in a decrease in vitamin D synthesis.&nbsp;&lt;strong&gt;Methodology:&lt;/strong&gt; This cross-sectional study was conducted at the Hereditary Blood Disorder Center in Ibn Al balady Hospital in Al Rusafa side in Baghdad from May to August 2023. The population of this study was children and adolescents diagnosed with beta-thalassemia major and on regular blood transfusions. Serum 25-OH-vitamin D, Serum calcium, and Serum ferritin were assessed in those patients.&nbsp;&lt;strong&gt;Result:&nbsp;&lt;/strong&gt;Out of 100 patients involved in this study, (38%) were children and (62%) were adolescents, the male-to-female ratio was 0.52. The mean age of the studied sample was 11.52±4.094 years. The mean 25-OH Vit D level was 24.94±14.66 ng/ml, only 23% of the patients had normal levels of serum vitamin D concentration, 56% had deficient levels and 21% had insufficient levels. The mean serum Ca level was 2.28±0.18 mmol/l, only 19% had low total serum calcium levels, 2% had high levels, and 79% had normal serum calcium levels. The mean serum ferritin level was 3940.48 ± 2287.76 ng/ml, no one had a normal serum ferritin level.&nbsp;&lt;strong&gt;Conclusion: &lt;/strong&gt;A high prevalence of 25 hydroxy vitamin D deficiency and insufficiency levels among thalassemia patients is found, so frequent monitoring and appropriate therapeutic interventions to maintain normal levels of serum vitamin D are indicated to improve bone health and quality of life of those patients. Also, high levels of serum ferritin were noted among those patients who need frequent follow-up and proper chelation therapy.&lt;/p&gt

Treatment outcome of 100 chronic myeloid leukemia patients using nilotinib as the 2nd line therapy

Background: Nilotinib is a potent and selective BCR-ABL inhibitor approved for use in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CML-CP) and in patients with CML-CP and accelerated phase (CML-AP) who are resistant to or intolerant of imatinib. Patients with imatinib-resistant CML, nilotinib treatment resulted in a significant proportion of patients achieving hematologic and cytogenetic responses in all phases of CML. Objectives: The aim of the present study was to assess the treatment outcomes in term of the molecular response rate of CML patients using Nilotinib as the second-line therapy after failure of imatinib therapy. Patients and Methods: A prospective study conducted between December 2014 and December 2016 in Baghdad Teaching Hospital and National Centre of hematology. A total of 100 patients, who were on nilotinib therapy as the second-line therapy, were enrolled in this study. The molecular response was assessed using real-time quantitative polymerase chain reaction (RQ-PCR). Major molecular response (MMR) was defined as the BCR-ABL1 of <0.1% by RQ-PCR. Results: The median age was 39 years, 59 were female and 41 were male. Fifty-three patients were classified as high-risk group, and 47 patients were as low risk. The BCR-ABL transcription level had a significant reduction from baseline at 3 months (P = 0.035) and the reduction from 3 months to 6 months was also statistically significant (P < 0.001). Comparing the patients who achieved MMR versus NO MMR, there was a significant association between low European Treatment and Outcome Study score and achieving MMR. An estimated 24 months overall survival (OS) is 95%. Conclusion: This study concluded that nilotinib is an effective therapeutic option for patients with CML-CP-resistant to imatinib therapy. Nilotinib treatment resulted in a high-OS rate and was well tolerated

Treatment Refractoriness in Chronic Lymphocytic Leukemia: Old and New Molecular Biomarkers

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Despite its indolent clinical course, therapy refractoriness and disease progression still represent an unmet clinical need. Before the advent of pathway inhibitors, chemoimmunotherapy (CIT) was the commonest option for CLL treatment and is still widely used in areas with limited access to pathway inhibitors. Several biomarkers of refractoriness to CIT have been highlighted, including the unmutated status of immunoglobulin heavy chain variable genes and genetic lesions of TP53, BIRC3 and NOTCH1. In order to overcome resistance to CIT, targeted pathway inhibitors have become the standard of care for the treatment of CLL, with practice-changing results obtained through the inhibitors of Bruton tyrosine kinase (BTK) and BCL2. However, several acquired genetic lesions causing resistance to covalent and noncovalent BTK inhibitors have been reported, including point mutations of both BTK (e.g., C481S and L528W) and PLCG2 (e.g., R665W). Multiple mechanisms are involved in resistance to the BCL2 inhibitor venetoclax, including point mutations that impair drug binding, the upregulation of BCL2-related anti-apoptotic family members, and microenvironmental alterations. Recently, immune checkpoint inhibitors and CAR-T cells have been tested for CLL treatment, obtaining conflicting results. Potential refractoriness biomarkers to immunotherapy were identified, including abnormal levels of circulating IL-10 and IL-6 and the reduced presence of CD27+CD45RO− CD8+ T cells

Targeting BTK in B Cell Malignancies: From Mode of Action to Resistance Mechanisms

The B cell receptor (BCR) signaling pathway plays a crucial role in B cell development and contributes to the pathogenesis of B cell neoplasms. In B cell malignancies, the BCR is constitutively active through both ligand-dependent and ligand-independent mechanisms, resulting in continuous Bruton tyrosine kinase (BTK) signaling activation, which provides a survival and proliferation advantage to the neoplastic clone. Among B cell malignancies, those in which the most significant results were obtained by treatment with BTK inhibitors (BTKi) include chronic lymphocytic leukemia, mantle cell lymphoma, lymphoplasmacytic lymphoma, and diffuse large B cell lymphoma. Covalent BTKi (namely ibrutinib, acalabrutinib, and zanubrutinib) functions by irreversibly blocking BTK through covalent binding to the cysteine residue 481 (Cys-481) in the ATP-binding domain. Despite the high efficacy and safety of BTKi treatment, a significant fraction of patients affected by B cell malignancies who are treated with these drugs experience disease relapse. Several mechanisms of resistance to covalent BTKi, including Cys-481 mutations of BTK, have been investigated in B cell malignancies. Non-covalent BTKi, such as pirtobrutinib, have been developed and proven effective in patients carrying both Cys-481-mutated and unmutated BTK. Moreover, targeting BTK with proteolysis-targeting chimeras (PROTACs) represents a promising strategy to overcome resistance to BTKi in B cell neoplasms

Do we need local guidelines for the diagnosis and management of immune thrombocytopenia in Iraq?

AIMS: Immune thrombocytopenia (ITP), also known as immune thrombocytopenic purpura, is an autoimmune disorder characterized by a low platelet count in the blood. This study aimed to assess the health infrastructure in Iraq regarding the diagnosis and management of patients with immune thrombocytopenia (ITP), with a focus on the use of guidelines in ITP management. SETTINGS AND DESIGN: This was a cross-sectional study carried out between October and November 2022 to assess ITP diagnosis, management, and the use of guidelines in 18 governorates in Iraq. MATERIALS AND METHODS: Invited to this study were 79 hematologists who were registered in the Iraqi Society of Hematology and who practiced in the 18 governorates. Out of the 79 hematologists, 65 participated in this survey. Data were collected using a questionnaire. STATISTICAL ANALYSIS USED: IBM SPSS 28 for Windows was used for the analysis and Microsoft Excel was used for creating the graphs. Descriptive statistics were presented in the form of numbers and percentages as all variables were categorical. RESULTS: The most requested routine tests were manual assessment of platelet count (83.1%), blood film (98.5%), virology screen (90.9%), connective tissue screen (85.9%), and prothrombin time and partial thromboplastin time (78.5%). More than 80% of the hematologists request bone marrow aspiration for the patients who have no response to the first-line treatment. Only the genetic test and the quantitative immunoglobulin level testing were available in the private sector both by (100%), while the other tests were available in both sectors. More than 85% treat the patients as outpatients. Active bleeding, not platelet count, was the indication for hospitalization for 60% of the hematologists. Corticosteroids were chosen as the first choice as initial treatment by (93.8%), intravenous immunoglobulin the second choice by (6.2%). In the second-line treatment, rituximab was chosen as the first choice by (75.3%), and eltrombopag as the second choice (65%). Only 83% of the hematologists referred to a guideline, and the American Society of Hematology guideline was the most referred to. CONCLUSIONS: These results showed the need to establish national guidelines for the Diagnosis and Management of Immune Thrombocytopenia in Iraq to be able to effectively treat the laboratory findings and physical symptoms of ITP in addition to address the patient's emotional and mental health needs