Molecular, Cytogenetic, and Hematological Analysis of Chronic Myeloid Leukemia Patients and Discovery of Two Novel Translocations

Abstract

Chronic myeloid leukemia (CML) is a disease of hematopoietic stem cells and is caused by the balanced translocations among the long arms of chromosomes 9 and 22, which are called the Philadelphia (Ph) chromosome. In this study, 131 CML patients were enrolled. Complete blood cell count was performed at the time of diagnosis for all the patients. Cytogenetic (karyotyping) examination using bone marrow samples was conducted on 76 CML patients for the confirmation of Ph-positive (9;22)(q34;q11) standard translocation, complex variant translocation, and additional chromosome abnormalities. FISH was performed on 38 patients for diagnostic purposes and on 39 patients for monitoring purposes. Twenty-two samples of CML patients were evaluated by reverse transcriptase PCR and real-time PCR for the patients who failed to respond against imatinib mesylate. In this study, 72 (54.96%) were males and 59 (45.03%) were females with a median age of 38.5 years. CBC values in the diagnosis process showed that 75 patients had high values of WBC being > 100 × 10 3 / μ l , while 71 (58.01) patients exhibited reduced values of hemoglobin, i.e., <10.00 mg/dl, and high values of PLTs > 100 were observed in 40 (30.53%) patients. Cytogenetic results show that standard translocation was developed in 63 (82.89%), development of complex variant translocations in 4 (5.32%), additional chromosomal abnormalities (ACAs) in 3 (3.94%), and ACAs together with complex variant translocations in 1 (1.31%) patient. At the time of diagnosis, 61 (92.95%) patients were in the chronic phase, 4 (5.63%) were in the accelerated phase, and only 1 (1.40%) was in the blast crisis. Out of twenty-two patients, only 6 CML patients who were shifted from imatinib mesylate to nilotinib showed BCR-ABL-positive amplification. However, only 7 out of twenty-one patients exhibit BCR-ABL gene values ≥ 1 after three months of follow-up when analyzed by the quantitative real-time PCR. In conclusion, we found a novel five-way translocation 46XX,t(1;2;2;17;9;22)(p36.3,q21;q11.2,q21,q34,q11.2) and a novel four-way complex variant translocation 48XY,+8(8;17)(9;22),+der(22)(q11.2;q23)(q34;q11.2) in the accelerated phase.

Prognostic and predictive implications of Sokal scoring system in newly diagnosed Chronic Myeloid Leukemia patients

“…At diagnosis, the clinicohematological parameters taken into account are listed in table-I. 12 At the time of the diagnosis, the risk categorization by the Sokal score included: 20 out of 62 patients (32%) as a lowrisk category, 34 patients (54.8%) as an intermediate-risk category, and 8 (12.9%) as a high-risk category. Table-II lists the proportion of patients falling into each risk category using the Sokal scoring system.…”

Cytogenetical and hematological analysis of chronic myelogenous leukemia patients with a novel case 52XX, t (1;9;22) (q23.3; q34; q11.2), +6, +8, i(9) (q10;q10), +18,+19,+21+der22 t(9;22)(q34;q11)

“…In addition, karyotypes were expressed by the International System for Human Cytogenetic Nomenclature. [ 9 ]…”

“…Trisomy 19 has been observed only in about 15% of CML cases. [6][7][8][9] Imatinib Mesylate (Gleevec) is an orally designed BCR/ABL protein tyrosine kinase inhibitor against BCR/ABL, platelet-derived growth factor receptor (PDGF-R), and c-kit. [10] This oral therapy is the first choice of treatment for almost 80% to 90% of CML patients of all phases.…”

Molecular relapse monitoring reveals the domination of impaired NK cell education over impaired inhibition in missing KIR‐ligand recognition in patients after unrelated hematopoietic stem cell transplantation for malignant diseases

“…[9][10][11] In recent years, significant advances have been made in the understanding of the molecular pathogenesis and early detection of relapse in acute and chronic leukemias and hematopoietic tumor progression after allo-HSCT. [12][13][14][15][16] By contrast, the hematological or morphological definition of relapse has lower sensibility and delayed detection. 17 As a result of different definitions of disease relapses and other heterogeneities of patients' cohorts in retrospective studies, conflicting results on KIR-ligand function have been reported posttransplant.…”

“…Early molecular diagnosis of relapse is both more sensitive and better suited to control immediate immunity from NK cells 9–11 . In recent years, significant advances have been made in the understanding of the molecular pathogenesis and early detection of relapse in acute and chronic leukemias and hematopoietic tumor progression after allo‐HSCT 12–16 . By contrast, the hematological or morphological definition of relapse has lower sensibility and delayed detection 17 .…”