scholarly journals Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 904-912
Author(s):  
Huma Amin ◽  
Suhaib Ahmed
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Blood Cell ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cross Sectional Study ◽  
Total Leukocyte Count ◽  
Rt Pcr ◽  
Cross Sectional ◽  
Cell Counts ◽  
Time Of Presentation

Abstract Background Depending on breakpoints of rearrangement different types of BCR–ABL fusion protein can be generated in patients of chronic myeloid leukemia (CML). The aim of this study is to observe frequencies of major transcripts in CML patients by reverse transcriptase polymerase chain reaction (RT-PCR) and their hematological features at the time of presentation. Materials and methods This cross sectional study was performed at Molecular Lab of Riphah International University, Islamabad from January to June 2019. Consecutive peripheral blood samples of 70 newly diagnosed CML patients in chronic phase were analyzed by RT-PCR to detect different BCR–ABL transcripts. Routine blood cell counts were assessed by an automated hematology analyzer. Results All samples expressed typical BCR–ABL rearrangement. Expression of either e14a2 or e13a2 transcript was detected in 38 (54%) and 30 (43%) patients, respectively. Coexpression of e13a2 + e14a2 was found in 2 (3%) patients. The mean total leukocyte count was higher in group expressing e13a2 (P = 0.01). Higher mean platelet count was noted in patients with e14a2 transcript, but this difference was statistically insignificant (P = 0.1). The association of male gender was observed with the group exhibiting e14a2 (P = 0.01). There was no statistically significant association between transcript type and different ranges of age, hemoglobin levels, and platelet and total leukocyte counts (P > 0.05). Conclusion e14a2 transcript was most common transcript in CML patients. Patients exhibiting e13a2 subgroup presented with significantly higher mean white blood cell count at the time of presentation. Significantly higher proportion of male patients was found to express e14a2 transcript over e13a2.

scholarly journals High STAT5A Expression is Associated with Major Molecular Response Achievement Failure of Chronic Phase Chronic Myeloid Leukemia Patients Receiving Hydroxyurea before Imatinib: A Cross-sectional Study

2021 ◽  
Vol 9 (B) ◽  
pp. 1160-1167
Author(s):  
Ikhwan Rinaldi ◽  
Anastasia Putri ◽  
Melva Louisa ◽  
Sukamto Koesnoe
Keyword(s):  
Logistic Regression ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cross Sectional Study ◽  
Molecular Response ◽  
Sectional Study ◽  
Major Molecular Response ◽  
Cross Sectional ◽  
Achievement Failure

BACKGROUND: STAT5 is a transcriptional factor which when highly expressed in chronic myeloid leukemia (CML) cells stimulate proliferation and mediate resistance from tyrosine kinase inhibitors, resulting in major molecular response (MMR) failure. STAT5 has two isoforms, STAT5A and STAT5B. However, prolonged use of imatinib appears to only upregulate STAT5A pathway. In addition, the resistance conferred by STAT5A does not extend to other drugs such as hydroxyurea. Hence, STAT5A and STAT5B might have different functions in CML cells. AIM: The objective of the study was to determine the association of STAT5A and STAT5B expression with MMR failure in CML patients. METHODS: This was a cross-sectional study of CML patients in chronic phase with age ≥ 18 years old, receiving IM therapy ≥ 12 months, and previously given hydroxyurea. MMR status was evaluated and patients were categorized as achieved or failed to achieve MMR. Expression levels of STAT5A and STAT5B were conducted using RT-PCR methods. Associations between STAT5A expression, STAT5B expression, hydroxyurea duration, and imatinib duration with MMR achievement were calculated using logistic regression. RESULTS: A total of 118 patients were analyzed; 71.1% failed to achieve MMR. Multivariate logistic regression analysis showed statistically significant association between high STAT5A expression (odds ratio [OR]: 3.852; 95% confidence interval [CI]: 1.420–10.452; p = 0.008), STAT5A/STAT5B interaction (OR: 0.150; 95% CI: 0.038–0.593; p = 0.007), longer hydroxyurea administration (OR: 3.882; 95% CI: 1.023–14.733; p = 0.046), and shorter imatinib administration (OR: 0.333; 95% CI: 0.132–0.840; p = 0.020) with MMR achievement failure. After adjusting STAT5A expression with STAT5A/STAT5B interaction, high STAT5A expression independently increased the likelihood of MMR achievement failure only in high expression STAT5B patients (OR: 3.852; 95% CI: 1.420–10.452; p = 0.008). CONCLUSION: High STAT5A expression which is induced by high STAT5B is associated with MMR achievement failure of chronic phase CML patients who received hydroxyurea before imatinib. Longer duration of hydroxyurea and shorter duration of IM confound of STAT5A expression to MMR achievement failure.

Chronic Myeloid Leukemia: Clinico-Hematological Profile from Southern Pakistan

2021 ◽  
Vol 15 (11) ◽  
pp. 3047-3053
Author(s):  
Sadia Sultan ◽  
Samar Abbas Jaffri ◽  
Rozina Zeeshan ◽  
Syed Muhammed Irfan
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Elevated Serum ◽  
Chronic Phase ◽  
Clinical History ◽  
Cross Sectional Study ◽  
Eligibility Criteria ◽  
Cross Sectional ◽  
Medical College ◽  
Chronic Myeloproliferative Disorder

Background: Chronic myeloid leukemia is a form of chronic myeloproliferative disorder described by the presence of specific haematological and cytogenetic markers. It is a very common blood neoplasm that usually requires a basic clinical history, review, and regular blood examination to diagnose. If detected early, it has a high cure rate. Objective: To assess the clinical and laboratory features of chronic phase chronic myeloid leukemia patients. Study Design: Cross-sectional study Place and Duration of Study: Department of Haematology, Liaquat National Hospital and Medical College, Karachi 1st January 2012 to 31st December 2016 Methodology: One hundred and forty four chronic myeloid leukemia patients visited the study site during this period, of which 132 were in the chronic phase and met the eligibility criteria. The patient’s data, including age, gender, clinical and laboratory parameters were obtained. Results: One hundred and fifteen (87.1%) had constitutional symptoms, predominantly fatigue and abdominal discomfort. The clinical presentation displayed splenomegaly among 89.3% of patients with a mean spleen span of 18.9±3.7 cm and massive splenomegaly in 32.5% of patients. Haematological presentation at baseline showed that the mean haemoglobin level of the enrolled patients was 9.6±2.0g/dl, TLC was 167.6±123.3x109/l, and platelet count was 398.7±281.9x109/l. Furthermore, 19.4%of patients were anaemic, and hyperleukocytosis was detected in 24.2%. High LDH, hyperuricemia and elevated serum creatinine were present in 38.6%, 40.9%, and 14.3%, respectively. Conclusion: Unlike the western countries, chronic myeloid leukemiais more prevalent in a very young age group in Pakistan. The chronic myeloid leukemia patients displayed variable clinical and haematological presentation. Constitutional symptoms and splenomegaly were consistent features among the majority of patients. Keywords: Chronic myeloid leukemia, Clinico-hematological, Pakistan

scholarly journals Concurrent Diagnosis of Chronic Myeloid Leukemia and Follicular Lymphoma: An Unreported Presentation

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Amy G. Starr ◽  
Sushma R. Jonna ◽  
Joeffrey J. Chahine ◽  
Bhaskar V. Kallakury ◽  
Chaitra S. Ujjani
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Follicular Lymphoma ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Mediastinal Lymphadenopathy ◽  
Pcr Analysis ◽  
Molecular Testing ◽  
Fish Analysis ◽  
Rt Pcr ◽  
Non Hodgkin Lymphoma

Lymphadenopathy in chronic myeloid leukemia (CML) is usually due to extramedullary involvement with accelerated or blast phases of the disease. The occurrence of non-Hodgkin lymphoma (NHL) as a synchronous malignancy with CML is rare. We report a case of a 73-year-old male who presented with dyspnea and right-sided lower extremity edema in the setting of leukocytosis. Bone marrow evaluation indicated a chronic phase chronic myeloid leukemia (CML), confirmed by molecular testing. Imaging of the chest for persistent dyspnea revealed supraclavicular and mediastinal lymphadenopathy. Biopsy of the cervical node showed expanded lymphoid follicles with atypical germinal centers that were positive for CD10, BCL-2, and BCL-6, consistent with follicular lymphoma (FL). Nodal PCR demonstrated clonal IGH and IGK gene rearrangements, and FISH analysis was positive for IGH-BCL-2 fusion. Together, these tests supported the diagnosis of FL. Additionally, the lymph node showed paracortical expansion by maturing pan-hematopoietic elements, no blastic groups, and positive RT-PCR analysis for BCR-ABL1, indicating concomitant involvement by chronic phase-CML. To our knowledge, this is the first reported case of a patient with a concurrent diagnosis of CML and FL.

Mutation Analysis of ABL1 Gene and its Relation to the Achievement of Major Molecular Response in Indonesian Chronic Myeloid Leukemia Patients

2020 ◽  
Vol 17 (1) ◽  
pp. 48-54
Author(s):  
Reni Widyastuti ◽  
Melva Louisa ◽  
Ikhwan Rinaldi ◽  
Riki Nova ◽  
Instiaty Instiaty ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Kinase Domain ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Cross Sectional ◽  
Imatinib Resistance

Background: Imatinib mesylate is the first tyrosine kinase inhibitor approved for chronic myeloid leukemia (CML) therapy. Imatinib is an effective drug. However, previous studies have shown that about 20-30% of patients eventually would develop resistance to imatinib. Approximately 40% of imatinib resistance is associated with BCRABL kinase domain mutation. One of the most common and serious variations account for imatinib response is T315I of ABL1 gene. Objective: The study aimed to examine the association of T315I mutation with the ABL1 gene and its relation to major molecular response (MMR) achievement in CML patients. This study also examined other mutations adjacent to T315I, i.e., F311I, F317L, and different possible variations in the ABL1 gene. Methods: This was a cross-sectional study on Indonesian CML patients in chronic phase. We analyzed 120 blood samples from patients in chronic phase who have received imatinib mesylate (IM) for ≥12 months. Results: There were no T315I, F311I, and F317L mutations found in this study. However, we found another variation, which was 36 substitutions from A to G at position 163816 of ABL1 gene (according to NG_012034.1). Conclusions: We found no T315I, F311I, and F317L mutations in this study. Our findings suggest that there might be other factors that influenced the MMR achievement in our study patients. However, there were 36 substitutions from A to G at position 163.816 (according to NG_012034.1) that needed further examination to explore the significance of this mutation in clinical practice.

scholarly journals Use of tyrosine kinase inhibitor by patients with chronic myeloid leukemia at a public hematology institution in the state of Amazonas, Brazil

2020 ◽  
Vol 11 (4) ◽  
pp. 510
Author(s):  
Andreia D. MENEZES ◽  
Nelson A. FRAIJI
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Cross Sectional Study ◽  
Chi Square ◽  
Cross Sectional ◽  
The Right

Objectives: To evaluate the conditions of use of tyrosine kinase inhibitors and adherence by patients with chronic myeloid leukemia treated at a public hematology institution. Methods: This was an observational and cross-sectional study carried out from December 2015 to April 2016. Data collection was carried out through interviews with standardized questionnaires that assessed the socioeconomic and demographic profile, drug therapy and by the Morisky-Green test that assessed the green adherence. Patients over 18 years old who had been using one of the tyrosine kinase inhibitors for more than one month were included; imatinib, dasatinib or nilotinib and who signed the informed consert form, agreement to participate in study. Descriptive statistical analysis and chi-square test with Yates correction were performed. Results: 63 patients were interviewed, with a mean age of 50 years with a standard deviation of 15.95. being 60% men. As for knowledge about the aspects related to the use of inhibitors: 95.2% took at the right time, 93.7% did not use other medications concomitantly, 63.5% kept it in an appropriate place and 97% of the patients received prior guidance from the doctor about the use. As for information about treatment, 90.5% knew the purpose of taking the medication, 60% did not know the time of use, 83% did not know what would happen if they stopped taking it and 73% believed they could stop the treatment at some point. Adherence to treatment was identified 46% of patients. Conclusion: No statistically significant differences were found between having or not adherence, when compared with the studied variables.

scholarly journals Comparison between CT and RT-PCR in a cohort of symptomatic patients with suspected COVID-19 pneumonia during the outbreak peak in Italy

2020 ◽  
Author(s):  
Giulia Besutti ◽  
Paolo Giorgi Rossi ◽  
Valentina Iotti ◽  
Lucia Spaggiari ◽  
Riccardo Bonacini ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Ground Glass ◽  
Reference Standard ◽  
Sectional Study ◽  
Rt Pcr ◽  
Cross Sectional ◽  
Oxygen Saturation Level ◽  
Blood Tests ◽  
Cell Counts ◽  
Italian Cohort

Abstract Objective: To assess sensitivity and specificity of CT vs RT-PCR for the diagnosis of COVID-19 pneumonia in a prospective Italian cohort of symptomatic patients during the outbreak peak.Methods: In this cross-sectional study we included all consecutive patients who presented to the ER between March 13th and 23rd for suspected COVID-19 and underwent both CT and RT-PCR within 3 days. Using a structured report, radiologists prospectively classified CTs in highly suggestive, suggestive, and non-suggestive of COVID-19 pneumonia. Ground-glass, consolidation, and visual extension of parenchymal changes were collected. Three different RT-PCR-based reference standard definitions were used. Oxygen saturation level, CRP, LDH, and blood cell counts were collected and compared between CT/RT-PCR classes.Results: The study included 696 patients (41.4% women; age 59±15.8 years): 423/454 (93%) patients with highly suggestive CT, 97/127 (76%) with suggestive CT, and 31/115 (27%) with non-suggestive CT had positive RT-PCR. CT sensitivity ranged from 73% to 77% and from 90% to 94% for high and low positivity threshold, respectively. Specificity ranged from 79% to 84% for high positivity threshold and was about 58% for low positivity threshold. PPV remained ≥90% in all cases. Ground-glass was more frequent in patients with positive RT-PCR in all CT classes. Blood tests were significantly associated with RT-PCR and CT classes. Leukocytes, lymphocytes, neutrophils, and platelets decreased, CRP and LDH increased from non-suggestive to suggestive CT classes.Conclusions: During the outbreak peak, CT presented high PPV and may be considered a good reference to recognize COVID-19 patients while waiting for RT-PCR confirmation.

The Association Between the Level of Leukemic Stem Cells and Treatment Response Among Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate

2020 ◽  
Vol 7 (2) ◽  
pp. 119-124
Author(s):  
Shinta Oktya Wardhani ◽  
Hani Susianti ◽  
Puji Rahayu ◽  
Yuyun Yueniwati
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Cross Sectional Study ◽  
Imatinib Therapy ◽  
Sectional Study ◽  
Cross Sectional ◽  
Blast Cells ◽  
Response Group

Background: The failure of imatinib therapy in patients with chronic myeloid leukemia (CML) is associated with the presence of leukemic stem cell (LSC), and the altered LSC level was reported to occur earlier in the progression of CML. Objective: The study aimed to assess the association between the level of LSC and treatment response among CML patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted in Saiful Anwar Hospital. All participants were divided into two groups, response and non-response group. To assess the level of LSC, flow cytometry was conducted conforming with BD Bioscience. The association and effect estimates were determined using multiple logistic regression. Results and Discussion: A total of 29 response and non-response CML patients treated with imatinib therapy were recruited for our study. After six months of imatinib therapy, we found that elevated levels of leukocytes, thrombocytes, basophils, and blast cells were associated with treatment failure among CML patients treated with imatinib. Moreover, we also found that the LSC level was observed significantly higher in the non-response group compared to the response group among CML patients treated with imatinib. Conclusion: Our study reveals that the elevated level of LSC is considered as an important factor to predict the failure of imatinib therapy among CML patients.

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