Browsing by Author "Djordjevic, Vesna (57215460423)"

Background and Objectives: With the advent of novel therapies for nucleophosmin gene (NPM1)-mutated acute myeloid leukemia (AML), there is a growing need for the reliable prediction of NPM1 mutations. This study explored the role of cytomorphological features in the early prediction of NPM1-mutated AML. Materials and Methods: Altogether, 212 de novo AML cases with normal karyotypes, diagnosed and treated at a single institution within 5 years (2018–2023), were retrospectively evaluated. A final diagnosis of NPM1-mutated AML, based on the World Health Organization (WHO) integrated criteria, including real-time based identification of NPM1 mutation and normal karyotype, was established in 83/212 (39.15%) cases. Results: Cup-like blasts (CLBs), a cytomorphological feature suggestive of NPM1-mutated AML, were detected in 56/83 (67%) patients. Most cases (44/56, 78.6%) had CLB ≥ 10%. In total, 27 of 83 AML NPM1-mutated patients had no CLB morphology (missed call). Additionally, two of 212 had CLB morphology without confirmed NPM1 mutation (wrong call). The positive/negative predictive values of cytomorphological evaluation for CLB ≥ 10% were 95.7%/75.6%, with sensitivity/specificity of 53%/98.5%, while the accuracy was 80.7%. We noted an increased percentage of CLBs (≥15%) in 77.8% and 50% of patients with AML without and with granulocytic maturation, respectively (the specificity for NPM1 mutation prediction was 100%). CLB was associated with fms-like tyrosine kinase 3 (FLT3) mutation (p = 0.03), but, without statistical significance for CLB ≥ 10% and CLB ≥ 15%. Conclusions: Our investigation confirmed that the morphological identification of CLB at diagnosis represents a reliable and easily reproducible tool for the early prediction of NPM1 mutations, enabling a streamlined genetic work-up for its confirmation. This may facilitate considering the early administration of individualized therapies by clinicians for specific patients. © 2024 by the authors.

Introduction. Additional karyotype abnormalities in the Philadelphia-positive (Ph+) clone can emerge during the progression of chronic myeloid leukemia (CML) and are of-ten associated with the resistance to treatment with tyrosine kinase inhibitors (TKI). Sometimes, during the TKI treat-ment, karyotype abnormalities can appear in the Philadelph-ia-negative (Ph-) cells as well but do not seem to adversely affect the outcome except for chromosome 7 abnormalities. Case report. The patient presented was in the chronic phase of Ph+ CML with highly diverse karyotype abnormal-ities. The abnormalities appeared in three unrelated clones during the TKIs treatment, followed by the evolution of the disease into acute myeloid leukemia (AML). The primary Ph+ clone was revealed during the chronic phase of CML, and therapy with imatinib mesylate was commenced. After a three-year hematologic and cytogenetic remission period, the evolution of the primary clone was noticed. Nilotinib was introduced, leading to a good molecular response and the disappearance/loss of the Ph+ clone with additional abnormalities but with the appearance of the Ph- clone with trisomy 8. Finally, after 5.5 years of nilotinib therapy, the Ph- clone with monosomy 7 occurred during the deep mo-lecular response for BCR-ABL. At that time, the FISH anal-ysis for trisomy 8 was negative, but the rise in blast count was noticed in the bone marrow, and the diagnosis of the secondary AML was established soon after. Conclusion. The achievement of the deep molecular response in CML patients does not rule out regular cytogenetic testing of their bone marrow. This is of crucial importance for detecting adverse karyotype abnormalities leading to the development of the myelodysplastic syndrome and AML. © 2021 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

This study explores cytomorphologic features and their predictive role for early identification of acute myeloid leukemia (AML) with morphological distinctive recurrent cytogenetic abnormalities (RCA): t(15;17), t(8;21) and inv(16)/t(16;16). We retrospectively evaluated 396 de novo AML cases, diagnosed and treated at single institution, between 2013-2017. Specific cytomorphologic features suggesting distinctive AML-RCA were revealed at diagnosis in 62 (15.65%) patients, including AML with t(15;17) in 41 (66.13%), t(8;21) in 13 (20.97%) and inv(16)/t(16;16) in 8 (12.90%). Final diagnoses of AML-RCA according to WHO integrated diagnostic criteria were established in 66 (16.66%) cases, including AML with t(15;17) 40 (60.60%), t(8;21) 17 (25.76%), and inv(16)/t(16;16) 9 (13.64%). Discordance between cytomorphological and other integrated criteria was detected as missed/wrong-call in 0/1 for t(15;17), 6/2 for t(8;21) and 2/1 for inv(16)/t(16;16). The cytomorphological accuracy was 97.56% (40/41) for t(15;17), 57.89% (11/19) for t(8;21) and 70% (7/10) for inv (16)/t(16;16). Positive/negative predictive values of cytomorphological evaluation were: 97.56%/100% for t(15;17); 84.62%/88.68% for t(8;21); 87.50%/96.65% for inv(16)/t(16;16). Sensitivity/specificity were: 100%/96.15% for t(15;17); 64.10%/95.92% for t(8;21); 77.78%/98.25% for inv(16)/t(16;16). We confirmed that morphology is still a highly relevant evaluation method in diagnosing several common AML-RCAs before completing cytogenetic and molecular studies, enabling early detection, particularly of AML with t(15;17). © 2018 Elsevier Ltd

This study explores cytomorphologic features and their predictive role for early identification of acute myeloid leukemia (AML) with morphological distinctive recurrent cytogenetic abnormalities (RCA): t(15;17), t(8;21) and inv(16)/t(16;16). We retrospectively evaluated 396 de novo AML cases, diagnosed and treated at single institution, between 2013-2017. Specific cytomorphologic features suggesting distinctive AML-RCA were revealed at diagnosis in 62 (15.65%) patients, including AML with t(15;17) in 41 (66.13%), t(8;21) in 13 (20.97%) and inv(16)/t(16;16) in 8 (12.90%). Final diagnoses of AML-RCA according to WHO integrated diagnostic criteria were established in 66 (16.66%) cases, including AML with t(15;17) 40 (60.60%), t(8;21) 17 (25.76%), and inv(16)/t(16;16) 9 (13.64%). Discordance between cytomorphological and other integrated criteria was detected as missed/wrong-call in 0/1 for t(15;17), 6/2 for t(8;21) and 2/1 for inv(16)/t(16;16). The cytomorphological accuracy was 97.56% (40/41) for t(15;17), 57.89% (11/19) for t(8;21) and 70% (7/10) for inv (16)/t(16;16). Positive/negative predictive values of cytomorphological evaluation were: 97.56%/100% for t(15;17); 84.62%/88.68% for t(8;21); 87.50%/96.65% for inv(16)/t(16;16). Sensitivity/specificity were: 100%/96.15% for t(15;17); 64.10%/95.92% for t(8;21); 77.78%/98.25% for inv(16)/t(16;16). We confirmed that morphology is still a highly relevant evaluation method in diagnosing several common AML-RCAs before completing cytogenetic and molecular studies, enabling early detection, particularly of AML with t(15;17). © 2018 Elsevier Ltd

A 56-year-old male with chronic idiopathic myelofibrosis and cytogenetic finding of 20q- after a period of 10 months developed acute Philadelphia-positive lymphoblastic leukemia. Immunophenotyping of peripheral blood by flow cytometry showed HLA-DR, CD34, CD19, CD22, CD10, CD33, and CD11b positivity. Cytogenetic analysis revealed the presence of 20q- and Philadelphia chromosome t(9;22)(q34:q11) at the time of disease transformation to ALL. The JAK2V617F mutation was not found. This is a very rare case of simultaneous presence of two cytogenetics abnormalities and evolution of primary idiopathic myelofibrosis to Philadelphia-positive acute lymphoblastic leukemia. © 2012 Elsevier GmbH.

A 56-year-old male with chronic idiopathic myelofibrosis and cytogenetic finding of 20q- after a period of 10 months developed acute Philadelphia-positive lymphoblastic leukemia. Immunophenotyping of peripheral blood by flow cytometry showed HLA-DR, CD34, CD19, CD22, CD10, CD33, and CD11b positivity. Cytogenetic analysis revealed the presence of 20q- and Philadelphia chromosome t(9;22)(q34:q11) at the time of disease transformation to ALL. The JAK2V617F mutation was not found. This is a very rare case of simultaneous presence of two cytogenetics abnormalities and evolution of primary idiopathic myelofibrosis to Philadelphia-positive acute lymphoblastic leukemia. © 2012 Elsevier GmbH.