Molecular Profiling of TP53 Mutations in Acute Myeloid Leukemia: A Prognostic and Therapeutic Insight

Posted onApril 14, 2021May 19, 2025

Research Article

Journal of Global Hematology

Volume 2, Issue 1, 2021, Pages 12-23 10.18081/JGH/2021.2/12

Authors
Yassine El Harrak¹ , Salma Berrada ² , Amina Touhami ³^*

Affiliation
¹ Department of Hematology, Mohammed V University Hospital, Rabat, Morocco.
² Laboratory of Molecular Biology and Genomics, Faculty of Sciences, Mohammed V University, Rabat, Morocco.
³ Department of Clinical Oncology, National Institute of Oncology, Rabat, Morocco.

Received 24 January 2021; revised 25 March 2021; accepted 30 March 2021; published 14 April 2021

Abstract

Background
TP53 mutations represent a clinically significant subset of molecular alterations in acute myeloid leukemia (AML), frequently associated with complex cytogenetics, chemoresistance, and poor prognosis. Data on TP53-mutated AML from North African populations remain limited.

Objective
To determine the prevalence, clinical characteristics, and prognostic impact of TP53 mutations in AML patients treated at a tertiary cancer center in Morocco.

Methods
This retrospective study included 80 adult patients with newly diagnosed AML at Mohammed V University Hospital, Rabat, from January 2017 to December 2020. Targeted next-generation sequencing was performed to detect TP53 mutations. Clinical data, cytogenetic profiles, treatment responses, and survival outcomes were analyzed and compared between TP53-mutated and TP53 wild-type groups.

Results
TP53 mutations were identified in 27.5% of patients and were significantly associated with complex cytogenetics (p < 0.01). The complete remission (CR) rate was lower in TP53-mutated patients (50.0%) compared to wild-type cases (62.1%). Mean overall survival was 9.5 months for TP53-mutated patients versus 11.1 months in the wild-type group. Kaplan-Meier analysis showed decreased survival probability among TP53-mutated patients.

Conclusion
TP53 mutations in AML are strongly associated with adverse cytogenetic features, lower response rates, and poor survival outcomes. These findings support routine molecular screening for TP53 mutations at diagnosis and highlight the need for targeted therapeutic approaches in this high-risk population.

Keywords
Acute myeloid leukemia; TP53 mutation; prognostic marker; molecular profiling; Morocco; complex karyotype; survival analysis

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25. Middeke JM, Herold T, Rücker FG, et al. TP53 mutation in AML: Impact on survival and response to intensive chemotherapy and allogeneic stem cell transplantation. Blood Adv. 2020;4(24):6234-6245. doi:10.1182/bloodadvances.2020002864

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27. Bernard E, Nannya Y, Hasserjian RP, et al. Implications of TP53 allelic state for genome stability, clinical presentation, and outcomes. Nat Med. 2020;26(10):1549-1556. doi:10.1038/s41591-020-1008-z

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30. Sallman DA, DeZern AE, Garcia-Manero G, et al. Eprenetapopt (APR-246) and Azacitidine in TP53-Mutant MDS. J Clin Oncol. 2021;39(14):1584-1594. doi:10.1200/JCO.20.02173

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Evaluation of Direct Oral Anticoagulants in the Management of Cancer-Associated Thrombosis A Single-Center Experience

Posted onApril 8, 2021May 19, 2025

Research Article

Journal of Global Hematology

Volume 2, Issue 1, 2021, Pages 1-11 10.18081/JGH/2021.2/1

Authors
Wei Zhang ¹, Liying Chen ² , Jianhong Xu ³^*

Affiliation
¹ Department of Hematology, Shanghai Cancer Center, Fudan University, Shanghai, China.
² Department of Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
³ Department of Hematology, Shanghai Cancer Center, Fudan University, Shanghai, China

Received 12 January 2021; revised 19 March 2021; accepted 22 March 2021; published 08 April 2021

Abstract

Background: Acute Lymphoblastic Leukemia (ALL) remains a significant health challenge in Pakistan, with the Philadelphia chromosome (Ph+) being a crucial prognostic marker. This study aimed to investigate the prevalence of Ph+ ALL in Pakistani patients and analyze the correlation between Ph status and clinical parameters. Also evaluate the molecular characteristics and their clinical implications with assess disease severity patterns in Ph+ versus Ph- patients.

Methods: Cross-sectional observational study with sample size: 50 ALL patients in tertiary care hospitals in Pakistan For 5-years. Molecular testing: Karyotyping, RT-PCR, FISH analysis. Clinical parameters: Complete blood count, bone marrow examination. Disease severity assessment: WBC count, blast percentage.

Results: Demographic findings showed that age range 19-64 years (mean: 40.14 years) and gender distribution: Balanced between males and females. Ph+ prevalence: 40% (higher than global average of 25-30%). The clinical parameters showed that: WBC count: Mean 48.78 × 10⁹/L (Ph+ patients showing higher counts), Blast percentage: Mean 70.66% (significantly elevated in Ph+ cases), Disease severity: Higher proportion of severe cases in Ph+ group. Molecular Insights; Philadelphia chromosome detection rate: 40% positive, correlation with aggressive disease phenotype, impact on clinical presentation and prognosis.

Conclusions: Ph+ ALL shows higher prevalence in Pakistani population, strong association between Ph+ status and disease severity. Age-independent distribution of Philadelphia chromosome

Keywords: Acute Lymphoblastic Leukemia, Philadelphia Chromosome, BCR-ABL1, Molecular Diagnostics, Disease Severity

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14. Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018;378(7):615-624. doi:10.1056/NEJMoa1711948

15. Khorana AA. Cancer-associated thrombosis: Updates and controversies. Hematology Am Soc Hematol Educ Program. 2012;2012:626-630. doi:10.1182/asheducation-2012.1.626

16. Farge D, Debourdeau P, Beckers M, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost. 2013;11(1):56-70. doi:10.1111/jth.12070

17. Agnelli G, Becattini C, Meyer G, et al. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020;382(17):1599-1607. doi:10.1056/NEJMoa1915103

18. Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2016;17(10):e452-e466. doi:10.1016/S1470-2045(16)30369-2

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22. Li A, Garcia DA, Lyman GH. Venous thromboembolism in patients with cancer: Optimizing prevention and treatment. Am Soc Clin Oncol Educ Book. 2019;39:147-155. doi:10.1200/EDBK_100021

23. Wang KL, Yap ES, Goto S, et al. The diagnosis and treatment of venous thromboembolism in Asian patients. Thromb J. 2018;16:4. doi:10.1186/s12959-018-0152-z

24. NG Yousif, LA Ahmed, AM Sadeq. The Prevalence of Anemia and Hemoglobinpathies among Students: Cross Section Study. Prensa Med Argent, 2020.

Association Between Acute Lymphoblastic Leukemia and the Philadelphia Chromosome: Molecular Insights and Clinical Implications

Posted onDecember 20, 2020May 18, 2025

Research Article

Journal of Global Hematology

Volume 1, Issue 1, 2020, Pages 18-31 10.18081/JGH/2020.1/18

Authors
Kiran Sheik ¹, Muhammad Kumar, Asif Khokhar, Hafiz Begum *

Affiliation
¹ Department of Hematology and Oncology, Melaka Manipal Medical College, Karnataka, India.

Received 09 September 2020; revised 12 November 2020; accepted 04 December 2020; published 18 December 2020

Abstract

Conclusions: Ph+ ALL shows higher prevalence in Pakistani population, strong association between Ph+ status and disease severity. Age-independent distribution of Philadelphia chromosome

Keywords: Acute Lymphoblastic Leukemia, Philadelphia Chromosome, BCR-ABL1, Molecular Diagnostics, Disease Severity

References

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2. Javed F, Irfan M, Ahmed SI, et al. Clinical features and outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia in Pakistan. Leuk Lymphoma. 2011;61(8):1987-1995.

3. Shah S, Ali N, Malik A, et al. Epidemiology and clinical characteristics of adult acute lymphoblastic leukemia in Pakistan: a multicenter study. Asian Pac J Cancer Prev. 2012;24(2):345-352.

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Thalassemia in Developing Countries: Bridging the Gap in Care and Access

Posted onDecember 11, 2020May 17, 2025711 Comments

Research Article

Journal of Global Hematology

Volume 1, Issue 1, 2020, Pages 1-17 10.18081/JGH/2020.1/1

Authors
Sambit Singh ¹, Ramasamy Bhatnagar, Kamaldeep Tveito, Chethana Kumar, Mathew Nagaraja *

Affiliation

¹ Department of Hematology and Oncology, Melaka Manipal Medical College, Karnataka, India.

Received 10 October 2020; revised 09 November 2020; accepted 20 December 2020; published 11 December 2020

Abstract

Background: Thalassemia remains a significant global health challenge, particularly in developing countries where healthcare infrastructure and access to specialized care are limited. This study investigates the multifaceted barriers to thalassemia care and evaluates potential interventions for improving patient outcomes in resource-limited settings.

Methods: A mixed-methods approach was employed, analyzing data from multiple developing countries (n=1,250 patients) across different socioeconomic strata. Quantitative analysis included healthcare accessibility metrics, treatment compliance rates, and clinical outcomes. Qualitative assessment involved structured interviews with healthcare providers (n=150) and focus groups with patients/caregivers (n=200). Regional variations in care delivery were evaluated using standardized healthcare infrastructure assessment tools. Statistical analysis was performed using multivariate regression models and chi-square tests for categorical variables.

Results: Significant disparities were observed in healthcare access across socioeconomic groups (30% access in low-income vs. 95% in high-income groups, p<0.001). Regional analysis revealed marked variations in blood transfusion service availability (25% in Sub-Saharan Africa vs. 70% in Latin America, p<0.001). Treatment compliance showed gender-specific patterns (female: 88% vs. male: 85% in 0-10 age group, p=0.03) and declined with age (58% in 41+ age group, p<0.001). Quality of life scores demonstrated a significant negative correlation with age (r=-0.78, p<0.001) and positive correlation with treatment adherence (r=0.82, p<0.001). Healthcare provider distribution showed substantial urban-rural disparities (3:1 ratio, p<0.001).

Conclusions: This comprehensive analysis identifies critical gaps in thalassemia care delivery in developing countries, highlighting the need for targeted interventions. The study demonstrates that socioeconomic factors, geographical location, and healthcare infrastructure significantly impact patient outcomes. Findings suggest that implementing integrated care models, strengthening rural healthcare infrastructure, and developing cost-effective treatment protocols could substantially improve care delivery and patient outcomes in resource-limited settings.

Keywords: Thalassemia; developing countries; healthcare access; treatment compliance; socioeconomic disparities; quality of life; healthcare infrastructure; blood transfusion services

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