European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia

Cross, Nicholas C. P.; Ernst, Thomas; Branford, Susan; Cayuela, Jean-Michel; Deininger, Michael; Fabarius, Alice; Kim, Dennis Dong Hwan; Machova Polakova, Katerina; Radich, Jerald P.; Hehlmann, Rüdiger; Hochhaus, Andreas; Apperley, Jane F.; Soverini, Simona

doi:10.1038/s41375-023-02048-y

Cited by 29 publications

(8 citation statements)

References 150 publications

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“…+ der (22)t(9; 22) and 9/9p are negatively predictive in adults with Philadelphia chromosome-positive ALL [31]. These finding was further explored in another study published in the American Journal of Haematology, which not only confirmed these negative manifestations but also discussed the challenge of the tyrosine kinase inhibitor-resistant population and emphasized the need for a more in-depth understanding of BCR-ABL kinases [32]. Furthermore a study shows the importance of identifying tyrosine kinase inhibitor protection mechanisms through genetic for the better treatment of CML [33].…”

Section: Discussionmentioning

confidence: 86%

Application of cytogenetic studies to assess relapse in patients after allogeneic bone marrow transplantation

2024

FEM

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Ergospirometry is a modern approach to the diagnosis of physical health that involves the use of exercise testing to measure cardiopulmonary function. Aims: To compare the distribution of health characteristics and their relationship between participants, to evaluate the accuracy of hypertension, hyperlipidemia and diabetes in both groups, to measure respiratory rate and heart rate between ergospirometric testing and traditional testing for physical health assessment. Study design: A comparative cross-sectional design to assess ergospirometric testing and traditional testing for physical health assessment. Methodology: The study employed a comparative cross-sectional design, utilizing convenience sampling to recruit participants for ergospirometric testing on a treadmill and the traditional 6-Minute Walk Test. Sample size determination yielded 100 participants (50 per group). Data on sociodemographic, comorbidities, and physiological parameters were collected and analyzed using descriptive statistics, chi-square tests, and independent sample t-tests. Results: The study compared Ergometric testing on a treadmill with the Traditional 6-Minute Walk Test across various parameters. Participants undergoing Ergometric testing were younger with more females and smokers, while the Walk Test group had higher BMI and exercise rates. Ergometric testing revealed higher rates of hypertension (P = 0.034) and hyperlipidemia (P = 0.021) but lower diabetes prevalence (P = 0.016). Additionally, Ergometric testing showed a better detection of respiratory parameters, exercise stress detection (P = 0.009), and cardiovascular parameters as compared to Traditional testing. Furthermore, it has a higher sensitivity 85% and specificity 80% compared to the traditional testing having sensitivity 75%, and specificity 70%. Scientific Novelty: Spirometry testing has made an impact on physical examination today; using advanced technology to achieve the best, sensitivity and specificity marks changes in the actual examination. Conclusion: Ergometric testing (treadmill) shows a significant advantage over traditional testing (6-Minute Walk Test) in diagnosing physical health conditions with a high sensitivity, specificity, and comprehensive parameter assessment.

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Section: Discussionmentioning

confidence: 86%

Application of cytogenetic studies to assess relapse in patients after allogeneic bone marrow transplantation

2024

FEM

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“…Overall, 17% of CML patients (n = 21) progressed to either AP-CML (n = 11) or BC-CML (n = 10). A study conducted and all approved TKIs in technologically advanced countries (2,3,13). Furthermore, there was a significant difference between chronic- and advanced-phase patients concerning male-to-female ratio, hemoglobin level, WBC count, and platelet count.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm of the hematopoietic stem cells (HSCs), marked by the uncontrolled excessive production of dysfunctional granulocytes and progenitors’ cells, in the bone marrow and peripheral blood (1). CML is the first aberrant chromosome abnormality described in a malignancy, known as the Philadelphia (Ph+) chromosome (2). The presence of Philadelphia chromosome t(9:22), which is a chromosomal reciprocal translocation between Abelson murine leukaemia (ABL) on the long arm of chromosome 9 and breakpoint cluster region (BCR) on chromosome 22, is a defining feature of CML (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…CML is the first aberrant chromosome abnormality described in a malignancy, known as the Philadelphia (Ph+) chromosome (2). The presence of Philadelphia chromosome t(9:22), which is a chromosomal reciprocal translocation between Abelson murine leukaemia (ABL) on the long arm of chromosome 9 and breakpoint cluster region (BCR) on chromosome 22, is a defining feature of CML (2,3). As a result of BCR-ABL1 fusion oncoprotein (P210) and the constitutive activity of tyrosine kinase, hematopoietic stem cells (HSC) are expanded clonally and CML is induced (4,5).…”

Section: Introductionmentioning

confidence: 99%

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Investigations on Clinical Validation of mutated ANKRD36 as a Novel Molecular Biomarker for Monitoring Early Progression and Timely Therapeutic Interventions in Blast Crisis CML

Alanazi,

Siyal,

Absar

et al. 2023

Preprint

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BackgroundChronic Myeloid Leukemia (CML) is initiated in the bone marrow due to the chromosomal translocation t(9;22), resulting in the fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have transformed fatal CML into an almost curable disease. However, TKIs lose efficacy during disease progression, and the mechanism of CML progression remains to be fully understood. Additionally, common molecular biomarkers for CML progression are lacking. Our studies previously detected ANKRD36 (c.1183_1184 delGC and c.1187_1188 dupTT) associated exclusively with advanced phase CML. However, clinical validation of this finding was pending. Therefore, this study aimed to clinically validate mutated ANKRD36 as a novel biomarker of CML progression.Materials and MethodsThe study enrolled 124 patients in all phases of CML, recruited from Mayo Hospital and Hameed Latif Hospital in Lahore, Punjab, between January 2020 and September 2023. All response criteria were adopted from the European LeukemiaNet guideline 2020. Informed consent was obtained from all study subjects. The study was approved by scientific and ethical review committees of all participating centers.Sanger sequencing was employed to detect ANKRD36 mutations in CML patients in accelerated phase (AP) (n=11) and blast crisis (BC) (n=10), with chronic-phase CML (CP-CML) patients as controls (n=103). Samples were processed using Big Dye Terminator Cycle Sequencing Ready Reaction kits and sequenced using ABI Prism 3730 Genetic Analyzer, and sequencing using forward and reverse primers for ANKRD36. Data was analyzed using SPSS version 26.ResultsDuring our study, 17% of CML patients progressed to advanced phases AP-CML n= 11 (8.9%) and BC-CML n=10 (8.1%). The chronic- and advanced-phase patients showed significant difference with respect to male-to-female ratio, hemoglobin level, WBC count, and platelet count. Sanger sequencing detected ANKRD36 mutations c.1183_1184 delGC and c.1187_1185 dupTT exclusively in all AP- and BC-CML patients but in none of the CP-CML patients. Nevertheless, mutations status was not associated with male-to-female ratio, hemoglobin level, WBC count, and platelet count, which makes ANKRD32 as an independent predictor of early and terminal disease progression in CML.ConclusionsThe study confirms ANKRD36 as a novel genomic biomarker for early and late CML progression. Further prospective studies should be carried out in this regard. ANKRD36, although fully uncharacterized in humans, shows the highest expression in bone marrow, particularly myeloid cells and correlation with high WBC count. Functional integrated genomic studies are recommended to further explore the role of ANKRD36 in the biology and pathogenesis of CML.

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“…The primary defining feature of CML for diagnosis is the presence of the BCR::ABL1 chimeric fusion oncogene, or Philadelphia chromosome (Ph), which arises from a t(9;22)(q34;q11) translocation between chromosomes 9 and 22 [ 2 ]. Based on the European LeukemiaNet (ELN) and MD Anderson (MDACC) criteria, CML progresses through three stages: chronic (CP), accelerated phase (AP), and blast crisis (BC), with each phase defined by increasing blast percentages, accumulation of additional cytogenic abnormalities, and other hematologic parameters [ 3 , 4 ]. However, since 2022, the World Health Organization (WHO) has removed the CML-AP designation and instead stratifies CML into CML-CP and CML-BP only, based on the presence of high-risk features [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia

Wu,

Liu,

Fruhstorfer

et al. 2024

IJMS

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Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22 within the hematopoietic stem cell compartment. The resultant fusion protein BCR::ABL1 is a constitutively active tyrosine kinase that can phosphorylate multiple downstream signaling molecules to promote cellular survival and inhibit apoptosis. Currently, tyrosine kinase inhibitors (TKIs), which impair ABL1 kinase activity by preventing ATP entry, are widely used as a successful therapeutic in CML treatment. However, disease relapses and the emergence of resistant clones have become a critical issue for CML therapeutics. Two main reasons behind the persisting obstacles to treatment are the acquired mutations in the ABL1 kinase domain and the presence of quiescent CML leukemia stem cells (LSCs) in the bone marrow, both of which can confer resistance to TKI therapy. In this article, we systemically review the structural and molecular properties of the critical domains of BCR::ABL1 and how understanding the essential role of BCR::ABL1 kinase activity has provided a solid foundation for the successful development of molecularly targeted therapy in CML. Comparison of responses and resistance to multiple BCR::ABL1 TKIs in clinical studies and current combination treatment strategies are also extensively discussed in this article.

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European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia

Cited by 29 publications

References 150 publications

Application of cytogenetic studies to assess relapse in patients after allogeneic bone marrow transplantation

Application of cytogenetic studies to assess relapse in patients after allogeneic bone marrow transplantation

Investigations on Clinical Validation of mutated ANKRD36 as a Novel Molecular Biomarker for Monitoring Early Progression and Timely Therapeutic Interventions in Blast Crisis CML

Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia

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