BCR-ABL Kinase Domain mutations - E255K, Y253 H and M351T among Sudanese population with CML

Khair, Hala Elsir; Elderdery, Abozer Y.; Nour, Bakri Yousef; Idris, Hadeil M. E.; Attaelmanan, Gamila Ali; Mohamed, Babker Ahmed; Waggiallah, Hisham Ali

doi:10.51847/mga8pfupad

Cited by 4 publications

(6 citation statements)

References 32 publications

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“…The most frequently found KD mutations in our cohort were G250E (18.3%, n = 11 of 60), T315I (10%, n = 6 of 60), F359I (8.3%, n = 5 of 60), and A399T, M244V, E255K, and F359V each detected in 6.7% ( n = 4 of 60) of patients. M351T was not detected in our study population, and this differs from data published from other African countries 22,23 …”

Section: Discussioncontrasting

confidence: 99%

“…M351T was not detected in our study population, and this differs from data published from other African countries. 22,23 The G250E KD mutation constitutes a substitution of glycine for glutamic acid at amino acid 250, positioned at the p-loop. The G250E mutation confers variable levels of resistance to most TKI's, but is sensitive to Dasatinib.…”

Section: Survival Analysismentioning

confidence: 99%

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Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa

Benjamin

Murugan

Hoosen

et al. 2023

Health Science Reports

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Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that harbors the Philadelphia chromosome. Tyrosine kinase inhibitor (TKI) therapy has dramatically improved the survival of patients with CML. Nevertheless, 20%-40% of CML patients require changes in TKI therapy due to intolerance or drug resistance. A total of 30%-60% of resistant cases result from kinase domain (KD) mutations.There is currently no published data on CML KD mutations in South Africa. Methods: This retrospective, descriptive study collected data from 206 CML patients attending the King Edward Hospital Hematology clinic. Patient-based and mutation-based factors were analyzed using descriptive statistical analysis and Kaplan-Meier curves for survival analysis. Results: KD mutations were detected in 29.1% (n = 60 of 206). A total of 40 different KD mutations were detected, with unknown responses to TKI therapy in 65% (n = 26 of 40). A total of 57.7% (n = 15 of 26) of mutations with an unknown response, showed a response to specific TKIs in our study. Four patients had A399T mutations, of which two showed good responses to Nilotinib. Patients with I293N and V280Mmutations showed good responses to Imatinib. G250E was most frequently detected. Despite M351T being one of six most commonly reported KD mutations globally, this mutation was not detected in our patient cohort. A total of 20.9%(n = 43 of 206) human immunodeficiency virus (HIV) positive patients were identified, of which 25.6% (n = 11 of 43) had KD mutations. HIV status showed no significant effect on mutational status or overall survival. Conclusion:The predicted response to TKI therapy was unknown in more than half of the KD mutations detected in our patient population. Additionally, eight patients with mutations with known responses to TKIs showed responses discordant to that expected. HIV status and KD mutations had no statistically significant effect on

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Section: Discussioncontrasting

confidence: 99%

Section: Survival Analysismentioning

confidence: 99%

Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa

Benjamin

Murugan

Hoosen

et al. 2023

Health Science Reports

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“…21 The study done in Sudan which included 99 CML patients, indicated that 44.4% were males and 55.6% females. 17 All CML patients at the start of the study showed CML-related anemia, the mean Hb (g/dl) was 9.27 ±1.43, which goes with findings of a study by Moura et al, 2019. 22 Regarding the mean WBCs (×103/μl) in the current study, it was estimated as 207.35 ±107.36.…”

Section: Discussionsupporting

confidence: 89%

“…In the current study, the mean age of the patients and controls was 48.22 ±8.85 and 48.33 ±10.0 years, respectively, which was similar to a study done in Sudan, included 99 CML patients; their mean age was 44.77. 17 In Africa the median age at diagnosis is <50 years, reflecting in part the lower median age of the population. 18 In addition, CML is an age-related neoplasm that commonly happens in older people.…”

Section: Discussionmentioning

confidence: 99%

sVCAM-1, and TGFβ1 in chronic phase, chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Hammed

Ahmed

Adam

et al. 2022

EJI

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The outcome for chronic phase (CP) chronic myelogenous leukemia (CML) patients has changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. We examined the characteristics of CML patients during TKI therapy by determining the plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), and transforming growth factor (TGFβ1) biomarkers. The plasma levels of sVCAM-1 and TGFβ1 were measured by ELISA at baseline and after 3 months of TKI treatment. The levels of sVCAM-1, and TGFβ1 were significantly elevated in patients with CML (P< 0.01). Dasatinib treatment was associated with a significant reduction in the levels of these biomarkers (P< 0.01). In conclusion, plasma levels of sVCAM-1 and TGFβ1 could have a role in the pathogenesis of CML and may be used as predictors of hematological and molecular responses to TKIs. A favorable outcome for Dasatinib therapy was observed.

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“…1 CML is characterized by increased proliferation and accumulation of the granulocytic cell line, without loss of differentiation. 2 BCR-ABL protein, a cancer-causing protein, has an active tyrosine kinase region of ABL, resulting in continuous cell growth and proliferation. 3 Imatinib was the first Food and Drug Administration (FDA, USA) approved tyrosine kinase inhibitors (TKIs) drug used as first-line treatment for newly diagnosed CML patients and those who were resistant or intolerant to interferon.…”

Section: Introductionmentioning

confidence: 99%

Kinetic of liver enzymes and serum electrolytes in HCV, HBV, and HIV negative chronic phase chronic myeloid leukemia patients treated with imatinib or nilotinib

Hammed

Nafady

Mohamed

et al. 2023

EJI

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The outcome for chronic phase (CP) chronic myeloid leukemia (CML) patients was changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. This study intended to evaluate side effects of TK Imatinib or Nilotinib on liver enzymes and serum electrolytes in relation to hematologic and molecular response in HCV-, HBV-, and HIV-, CP-CML patients. The study was a quasi-experimental pre-post single group design, included 38 HCV-, HBV-, and HIV-newly diagnosed Philadelphia positive CP-CML patients with normal hepatic and renal function. They were divided equally into two groups, 19 received Nilotinib, and 19 received Imatinib. Hematologic, BCR-ABL gene expression by RT-PCR, electrolytes and liver enzymes were measured at baseline and after 6 months of treatment. Patients age ranged between 20 and 62 years. Anemic manifestations represented the highest rate (n=23, 60.5%). The mean WBCs count was significantly reduced after treatment (p<0.001). The WBCs count was significantly reduced in the Nilotinib group than the Imatinib group (97% and 94%, respectively, p=0.049). The mean hemoglobin level was significantly increased after treatment (p=0.010). The mean platelet level did not change over the treatment period. The mean AST, ALT, and ALP levels were significantly increased after treatment, (p=0.014, p=0.002, and p=0.047, respectively). The ALP level was significantly increased in both groups (p=0.001). The mean sodium potassium, phosphorous, and calcium level was not changed over the treatment period. The mean BCR-ABL gene expression was sharply decreased after treatment (p<0.001). A higher reduction was observed in the Nilotinib group (99%) than the Imatinib group (91.5%) (p=0.025). Imatinib resulted in rise of AST and ALP levels than Nilotinib, while both had the same effect on the ALT level. Higher reduction in BCR-ABL gene expression was achieved by Nilotinib. Nilotinib and Imatinib did not affect serum levels of sodium, potassium, phosphorous, or calcium.

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BCR-ABL Kinase Domain mutations - E255K, Y253 H and M351T among Sudanese population with CML

Cited by 4 publications

References 32 publications

Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa

Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa

sVCAM-1, and TGFβ1 in chronic phase, chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Kinetic of liver enzymes and serum electrolytes in HCV, HBV, and HIV negative chronic phase chronic myeloid leukemia patients treated with imatinib or nilotinib

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