scholarly journals FEATURES OF DETECTING CYTOGENETIC AND MOLECULAR-GENETIC ABNORMALITY IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA USING VARIOUS METHODS

2021 ◽  
pp. 118-118
Author(s):  
S.Y. Pseush ◽  
L.V. Zozulya ◽  
L.L. Mikhaleva
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Genetic Abnormality

scholarly journals The Role of Molecular Genetic Translocations in the Initial Response to the Treatment under the ALLIC BFM 2009 Program in Children Patients with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 6 (3) ◽  
pp. 162-169
Author(s):  
O. A. Vynnytska ◽  
◽  
O. I. Dorosh ◽  
L. Ya. Dubey ◽  
N. V. Dubey
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Correlation Analysis ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Primary Response ◽  
Chromosomal Translocations ◽  
Induction Treatment ◽  
Blast Cells

The correlation analysis between the number of blast cells in bone marrow and peripheral blood was performed, and the dependence of blast percentage on the presence of molecular genetic translocations (AF4/MLL, BCR/ABL1, TEL/AML, E2A/PBX1) in patients with acute lymphoblastic leukemia (ALL) under the conditions of ALLIC-BFM 2009 cytostatic therapy was researched. The purpose of the study was to establish a relationship between the number of blast cells in bone marrow and peripheral blood depending on the presence of molecular genetic translocations for early detection of induction treatment by ALLIC BFM 2009. Materials and methods. The survey group consisted of 105 children aged 12 months to 16 years (median age was 6 years). Among those surveyed were 62 boys (59.0%) and 43 girls (41.0%). All patients were diagnosed with acute lymphoblastic leukemia. Results and discussion. Correlation analysis revealed a high degree of correlation between the number of blast cells in the bone marrow and peripheral blood, as the correlation coefficient (r) is 0.87. It is shown that the increase in the number of blast cells depends on the presence of chromosomal translocations. The highest number of blasts was observed in patients with BCR/ABL1 and E2A/PBX1 translocations, in whom the content of blasts in bone marrow was 97 and 96%, respectively, and in peripheral blood - 67 and 73%, respectively. It was found that treatment under the ALLIC BFM 2009 program leads to a decrease in the number of blast cells in the bone marrow and blood with minimal values on the 33rd day of treatment. It has been shown that the highest levels of blast cells during chemotherapy are observed in patients with chromosomal translocations BCR/ABL1 and E2A/PBX1. In patients with AF4/MLL translocation, the efficacy of therapy was the highest because no blast cells in the bone marrow were visualized on day 33 of treatment. The study of the primary response of patients with acute lymphoblastic leukemia to induction treatment according to the ALLIC BFM 2009 program revealed the dependence of the level of blast cells of bone marrow and blood on the type of chromosomal aberration. Patients with BCR/ABL1 and E2A/PBX1 have the highest resistance to chemotherapy with molecular genetic translocations, and patients with AF4/MLL and TEL/AML have the lowest resistance, as evidenced by the presence and absence of blast cells in the peripheral blood, respectively. Conclusion. Establishing the relationship between cytogenetic and molecular genetic features of the tumour clone will help determine the degree of malignancy of the process, as well as the risk group for the course of the disease. Determining the dependence of acute leukemia on molecular genetic translocations will make it possible to further modify the treatment program

scholarly journals The Clinical Utility of Optical Genome Mapping for the Assessment of Genomic Aberrations in Acute Lymphoblastic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4388
Author(s):  
Jonathan Lukas Lühmann ◽  
Marie Stelter ◽  
Marie Wolter ◽  
Josephine Kater ◽  
Jana Lentes ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Copy Number ◽  
Genome Mapping ◽  
Lymphoblastic Leukemia ◽  
Complex Structure ◽  
Molecular Genetic ◽  
Copy Number Variations ◽  
Pediatric All ◽  
Genomic Aberrations ◽  
Unknown Gene

Acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer occurring in children. ALL is characterized by structural and numeric genomic aberrations that strongly correlate with prognosis and clinical outcome. Usually, a combination of cyto- and molecular genetic methods (karyotyping, array-CGH, FISH, RT-PCR, RNA-Seq) is needed to identify all aberrations relevant for risk stratification. We investigated the feasibility of optical genome mapping (OGM), a DNA-based method, to detect these aberrations in an all-in-one approach. As proof of principle, twelve pediatric ALL samples were analyzed by OGM, and results were validated by comparing OGM data to results obtained from routine diagnostics. All genomic aberrations including translocations (e.g., dic(9;12)), aneuploidies (e.g., high hyperdiploidy) and copy number variations (e.g., IKZF1, PAX5) known from other techniques were also detected by OGM. Moreover, OGM was superior to well-established techniques for resolution of the more complex structure of a translocation t(12;21) and had a higher sensitivity for detection of copy number alterations. Importantly, a new and unknown gene fusion of JAK2 and NPAT due to a translocation t(9;11) was detected. We demonstrate the feasibility of OGM to detect well-established as well as new putative prognostic markers in an all-in-one approach in ALL. We hope that these limited results will be confirmed with testing of more samples in the future.

The Recurrent SET-NUP214 Fusion as a New HOXA Activation Mechanism in Pediatric T-Cell Acute Lymphoblastic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 233-233 ◽  
Author(s):  
Pieter Van Vlierberghe ◽  
Joelle Tchinda ◽  
Martine van Grotel ◽  
Charles Lee ◽  
H. Berna Beverloo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Transcriptional Activation ◽  
Chromosomal Abnormalities ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Activation Mechanism ◽  
Fusion Product ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Hoxa Genes

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is mostly characterized by specific chromosomal abnormalities, some occurring in a mutually exclusive manner possibly delineating specific T-ALL subgroups. One subgroup, including MLL-rearranged, CALM-AF10 or inv(7)(p15q34) cases, is characterized by elevated expression of HOXA genes. Using a gene expression based clustering analysis of 67 T-ALL cases with recurrent molecular genetic abnormalities and 25 samples lacking apparent aberrations, we identified 5 new cases with elevated HOXA levels. Using array-CGH, a cryptic and recurrent deletion, del(9)(q34.11q34.13), was exclusively identified in 3 of these 5 cases. This deletion results in a conserved SET-NUP214 fusion product, that was also identified in the T-ALL cell line LOUCY. SET-NUP214 binds in the promoter regions of specific HOXA genes, where it interacts with CMR1 and DOT1L leading to the transcriptional activation of HOXA genes. Targeted inhibition of SET-NUP214 by siRNA abolished expression of HOXA genes, inhibited proliferation and induced differentiation in LOUCY but not in other T-ALL lines. We conclude that SET-NUP214 contributes to the pathogenesis of T-ALL by enforcing T-cell differentiation arrest.

scholarly journals Diagnostics and treatment challenges of Ph-like acute lymphoblastic leukemia: a description of 3 clinical cases

2018 ◽  
Vol 90 (7) ◽  
pp. 110-117
Author(s):  
K I ZARUBINA ◽  
E N PAROVICHNIKOVA ◽  
G A BASKHAEVA ◽  
A E KRASILNIKOVA ◽  
O A GAVRILINA ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Biological Properties ◽  
Diverse Group ◽  
Blood Disorders ◽  
Selective Treatment ◽  
Genetic Techniques ◽  
Clinical Cases

B-cell acute lymphoblastic leukemia (B-ALL) is a diverse group of malignant blood disorders both with regard to the biological properties of the tumor and to therapeutic approaches. Immunophenotyping, molecular genetic techniques, whole-genome sequencing characterize B-ALL as a very diverse group for sensitivity to chemotherapy and prognosis. We present three clinical cases of patients with B-ALL and expected good response to standard therapy, in whom standard protocol treatment failured: refractoriness, persistence of minimal residual disease (MRD), and progression (MRD increase). The remission in these patients was achieved after chemotherapy change to immunological targeted therapy. Nowadays a unified therapeutic approach to all primary patients of the B-ALL is considered generally outdated. Great efforts are carrying out to develop molecular genetic classifications. The molecular dissection of subtypes of B-ALL goes on, and new protocols for selective treatment with targeting are clearly outlined for each subtype of B-ALL.

scholarly journals Immunophenotypic characteristics of early T-cell precursor acute lymphoblastic leukemia

2019 ◽  
Vol 18 (2) ◽  
pp. 66-74
Author(s):  
A. S. Sharlai ◽  
O. I. Illarionova ◽  
Y. G. Fediukova ◽  
T. Yu. Verzhbitskaya ◽  
L. G. Fechina ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Antigen Expression ◽  
Control Group ◽  
Study Group ◽  
Cell Precursor ◽  
Pediatric Hematology ◽  
National Medical

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized T-ymphoblastic leukemia subgroup with poor prognosis and high-risk of relapse. ETP-ALL subgroup is characterized by unique gene expression and particular cell surface markers profile. Nevertheless, this group cannot be easily detected due to its biological heterogeneity. The aim of the present study was to explore the immunophenotypic characteristics of early T-cell precursor acute lymphoblastic leukemia in ETP-ALL patient. The study group consisted of 64 patients with ETP-ALL. 380 patients with other variants of T-ALL were included to the control group. The antigen expression profile was assessed by multicolor flow cytometry. TI and TII immunological variants were detected in the group of patients with ETP-ALL. Cell markers expression level was determined in both groups. In the study group of ETP-ALL patients CD11a expression was more specific to TII-ALL, while CD33 expression – for TI-ALL. This study allowed to characterize group of patients with ETP-ALL and detected immunophenotypic heterogeneity. More interlaboratory studies are needed for understanding immunological and molecular genetic features ETP-ALL. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology.

MOLECULAR GENETIC CLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) OF CHILDHOOD AND INFANCY

1989 ◽  
Vol 11 (1) ◽  
pp. 116
Author(s):  
Carolyn A. Felix ◽  
Ilan R. Kirsch ◽  
Gregory H. Reaman ◽  
Stanley K. Korsmeyer ◽  
Diane E. Cole ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Genetic Classification

scholarly journals The molecular genetic makeup of acute lymphoblastic leukemia

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 389-396 ◽  
Author(s):  
Charles G. Mullighan
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Stratification ◽  
Treatment Failure ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Receptor Gene ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Genomic Profiling

Abstract Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention. Mutations in genes regulating lymphoid development are a hallmark of ALL, and alterations of the lymphoid transcription factor gene IKZF1 (IKAROS) are associated with a high risk of treatment failure in B-ALL. Approximately 20% of B-ALL cases harbor genetic alterations that activate kinase signaling that may be amenable to treatment with tyrosine kinase inhibitors, including rearrangements of the cytokine receptor gene CRLF2; rearrangements of ABL1, JAK2, and PDGFRB; and mutations of JAK1 and JAK2. Whole-genome sequencing has also identified novel targets of mutation in aggressive T-lineage ALL, including hematopoietic regulators (ETV6 and RUNX1), tyrosine kinases, and epigenetic regulators. Challenges for the future are to comprehensively identify and experimentally validate all genetic alterations driving leukemogenesis and treatment failure in childhood and adult ALL and to implement genomic profiling into the clinical setting to guide risk stratification and targeted therapy.

Inv(11)(q21q23); KMT2A-MAML2, a Recurrent Genetic Abnormality in T-Cell Therapy–related Acute Lymphoblastic Leukemia

2020 ◽  
Vol 42 (4) ◽  
pp. e258-e261
Author(s):  
Rachel A. Mariani ◽  
Mercedes Silva ◽  
Edward Caparelli ◽  
Lawrence J. Jennings ◽  
Kai Lee Yap ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
Lymphoblastic Leukemia ◽  
Genetic Abnormality ◽  
T Cell Therapy
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