ABSTRACT
AIM: To determine ways of formation of abnormal karyotypes in two clinical cases of secondary acute leukemias of myeloid and lymphoid lineages. MATERIAL AND METHODS: Bone marrow cells of one patient with therapy-related acute monoblastic/monocytic leukemia and one patient with therapy-related acute lymphoblastic leukemia were examined by cytogenetic GTG banding technique. RESULTS: An unusually large number of quantitative and structural anomalies of chromosomes in therapy-related acute monoblastic/monocytic leukemia have been established, which have many features in common with chromothripsis, namely instability of clones that manifested itself through quantitative anomalies (trisomy, monosomy, marker chromosomes, including chromosome 5), structural - t(9;11), deletions of the long arm of chromosomes 8 and 14, derivatives of chromosomes 3 and 7, ring chromosomes. In case of secondary acute lymphoblastic leukemia, the anomalous clone with balanced translocation in all 20 metaphase plates 46,XX,t(1;15)(p21;q24) has been registered, which is not described in the literature. Therefore, the diagnostic and prognostic value of such anomaly is unknown. CONCLUSIONS: Rearrangement with the involvement of the locus 11q23 was recorded in the case of chemotherapy treatment without topoisomerase II inhibitors. The complex karyotype formed after chemotherapy and radiotherapy, which is a criterion for an unfavorable prognosis of the disease, is considered as the equivalent of chromothripsis. t(1;15) is considered as an abnormality that can be attributed to the group of favorable secondary acute lymphoblastic leukemia prognosis.
Subject(s)
Abnormal Karyotype , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Leukemia, Monocytic, Acute/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Aged , Bone Marrow Cells/pathology , Bone Marrow Cells/physiology , Female , Humans , Leukemia, Monocytic, Acute/chemically induced , Leukemia, Monocytic, Acute/therapy , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Translocation, GeneticABSTRACT
AIM: Genetic inborn along with acquired diseases arise due to the lesions in genome of multipotent hematopoietic stem cells. The aim was to study an influence of constitutional anomaly, Klinefelter syndrome, and additional structural rearrangements on the BCR-ABL tyrosine kinase inhibitor targeted therapy efficacy. MATERIAL AND METHODS: We describe a 32-year-old male patient with chronic myeloid leukemia (CML) who was detected to have sex chromosomal abnormality during evaluation for Philadelphia chromosome. RESULTS: At diagnosis of CML, two clones were detected by standard cytogenetic investigation of bone marrow cells: 1) clone with translocation t(9;22)(q34;q11), with two sex X chromosomes and absence sex chromosome Y; 2) clone with t(9;22) and unbalanced t(Y;20)(q11;q13). Analysis of blast transformed lymphocytes from peripheral blood showed karyotype 47,XXY. Monitoring of targeted therapy with second generation inhibitor of BCR-ABL tyrosine kinase indicated a cytogenetic remission and absence of BCR-ABL1 fusion signals after 11 months. CONCLUSIONS: Absence of translocation t(9;22)(q34;q11) in blast transformed T-lymphocytes at diagnosis of CML evidences that this translocation may appear not only at the level of multipotent haemopoietic cell progenitors but also may have oligo lineage myeloid origin. Presence of additional structural chromosomal abnormality in the clone with t(9;22)(q34;q11) does not affect the efficacy of therapy with the use of second generation BCR-ABL tyrosine kinase inhibitor.
Subject(s)
Klinefelter Syndrome/complications , Klinefelter Syndrome/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Adult , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Bone Marrow Cells/pathology , Fusion Proteins, bcr-abl/antagonists & inhibitors , Fusion Proteins, bcr-abl/genetics , Humans , Karyotype , Klinefelter Syndrome/drug therapy , Klinefelter Syndrome/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Lymphocytes/drug effects , Lymphocytes/metabolism , Lymphocytes/pathology , Male , Protein Kinase Inhibitors/therapeutic use , Translocation, GeneticABSTRACT
Galectines are a family of carbohydrate-binding proteins with an affinity for beta-galactosides. Galectines is differentially expressed by various normal and pathological tissues and appears to be functionally polyvalent, with a wide range of biological activity. The intracellular and extracellular activity of galectines has been described. Evidence points to galectin and its ligands as one of the master regulators of such immune responses as T-cell homeostasis and survival, T-cell immune disorders, inflammation and allergies as well as host-pathogen interactions. Galectines expression or overexpression in tumors and/or the tissue surrounding them must be considered as a sign of the malignant tumor progression that is often related to the long-range dissemination of tumoral cells (metastasis), to their dissemination into the surrounding normal tissue, and to tumor immune-escape. Elevated levels of galectines have been found to be significantly associated with higher risk progressing of the lymphoproliferative disease. The targeted inhibition of Galectines expression is what should be developed for therapeutic applications against cancer progression. Galectines are the promising molecular target for the development of new and original diagnostic and therapeutic tools.
