scholarly journals Leukemia risk and the pattern of dose accumulation. Part 1: Characteristics of the study group of the Mayak Production Association personnel

2020 ◽  
Vol 12 (4) ◽  
pp. 18-28 ◽  
Author(s):  
Svetlana F. Sosnina ◽  
Pavel V. Okatenko ◽  
Aleksandr M. Yurkin ◽  
Susanna A. Rogacheva ◽  
Elena A. Gruzdeva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Radiation Exposure ◽  
Myeloid Leukemia ◽  
Production Association ◽  
Lymphoid Leukemia ◽  
Hematological Cancer ◽  
Red Bone Marrow ◽  
Cancer Pathology ◽  
Mayak Production Association ◽  
Hemopoietic System

Results of development of the database “Leukemia in the cohort of workers of the Mayak Production Association employed in 1948-1958” that was developed in the Laboratory of Radiation Epidemiology of Southern Urals Biophysics Institute were presented. The database contains hematological, clinical and dosimetric information for the workers of main plants of the first production facility of Soviet atomic industry employed in the period of production development – 1948-1958. The computer database contains information for two groups of Mayak Production Association workers: main group of workers with leukemia as the main cause of death (n=84) and group of personnel without hematological cancer pathology for comparison (n=300). The comparison group was composed in such a way to allow 3-4 controls of corresponding gender, age of exposure start, accumulated dose of external gamma-exposure to red bone marrow for each leukemia case. Methods of data collection and sources of medical data were described. Characteristics of software developed for the database was presented. The database containing a total of 19593 results of blood tests reflects dynamics of hematological values in atomic facility personnel due to prolonged radiation exposure. The range of accumulated absorbed doses of external gamma-exposure to red bone marrow in the group of personnel with leukemia diagnoses was 0.001-4.96 Gy; average dose for males was 1.24 Gy and 0.61 Gy – for females. Similar range is observed in the group of personnel without leukemia outcomes. Alongside differences in accumulation rates of external radiation exposure doses is evident: in the group of workers with hematological cancer pathology the average period of radiation exposure at production facility was 14.3 years for males and 12.1 years for females; in the comparison group – 20.4 and 13.9 years, respectively. Most leukemia cases were diagnosed in the workers of radiochemical facility (54.8%). Myeloid leukemia prevailed (47.6%) in the leukemia structure; among them acute myeloid leukemia made more than a half of the cases; lymphoid leukemia was diagnosed in 14.3% cases with prevailing role of chronic lymphoid leukemia. Acute and chronic monocytic leukemia were the rarest types of malignant neoplasms of hematopoietic tissue. Possible correlation between hematological values with individual doses of external gamma- and internal alpha-exposure (incorporated Pu-239) distributed over time was stated. The database allows calculating integrated leukocytic indices reflecting response of hemopoietic system to radiation exposure, tracking changes in hemopoiesis in proportion to accumulated dose to red bone marrow, analyzing specific characteristics of rehabilitation of hematological alterations after occupational contact to ionizing radiation is terminated. Information on acute and chronic diseases available for the workers in the database allows excluding non-specific response of hemopoietic system caused by associated pathology. A revision of leukemia risk estimated in the relation to dose rate for personnel exposed to chronic radiation could be regarded as one of perspective trends in using the database.

scholarly journals CREB: A Key Regulator of Normal and Neoplastic Hematopoiesis

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Salemiz Sandoval ◽  
Martina Pigazzi ◽  
Kathleen M. Sakamoto
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Cellular Proliferation ◽  
Leukemia Cell ◽  
Cellular Transformation ◽  
Camp Response Element Binding ◽  
Lymphoid Leukemia ◽  
Leukemia Cell Lines

The cAMP response element-binding protein (CREB) is a nuclear transcription factor downstream of cell surface receptors and mitogens that is critical for normal and neoplastic hematopoiesis. Previous work from our laboratory demonstrated that a majority of patients with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) overexpress CREB in the bone marrow. To understand the role of CREB in leukemogenesis, we examined the biological effect of CREB overexpression on primary leukemia cells, leukemia cell lines, and CREB overexpressing transgenic mice. Our results demonstrated that CREB overexpression leads to an increase in cellular proliferation and survival. Furthermore, CREB transgenic mice develop a myeloproliferative disorder with aberrant myelopoiesis in both the bone marrow and spleen. Additional research from other groups has shown that the expression of the cAMP early inducible repressor (ICER), a CREB repressor, is also deregulated in leukemias. And, miR-34b, a microRNA that negative regulates CREB expression, is expressed at lower levels in myeloid leukemia cell lines compared to that of healthy bone marrow. Taken together, these data suggest that CREB plays a role in cellular transformation. The data also suggest that CREB-specific signaling pathways could possibly serve as potential targets for therapeutic intervention.

Subacute Course of Chronic Radiation Syndrome Caused External Non-Uniform Radiation Exposure of Lost Source

2021 ◽  
Vol 66 (4) ◽  
pp. 62-69
Author(s):  
I. Galstyan ◽  
A. Bushmanov ◽  
Nelya Metlyaeva ◽  
V. Solov'ev ◽  
L. Mershin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ionizing Radiation ◽  
Acute Leukemia ◽  
Radiation Exposure ◽  
Total Dose ◽  
Tooth Enamel ◽  
Radiation Dermatitis ◽  
Radiation Beam ◽  
Red Bone Marrow ◽  
Chronic Radiation

Purpose: To analyze the features of the clinical course of chronic radiation syndrome (CRS) due to external non-uniform chronic exposure to prolonged household contact with a lost source of ionizing radiation. Material and methods: Analysis of 2 clinical observations of patients who developed subacutecourse of CRS and chronic radiation dermatitis due to external non-uniform exposure of the lost sources of ionizing radiation are presented. Results: Boy A. K. from the age of 1 year for 7 years was external radiation exposed (for 1.5 years non-uniform exposure ) to the total dose according EPR tooth enamel about 6.3 Gy, according to the data of retrospective dose recovery on red bone marrow using voxel modeling – 26 (19–37) Gy. F. V. V., male, 38 years, was external non-uniform radiation exposed for 5 months, the total dose according cytogenetic studies of 7.9 Gy (dose rate about 0.035 Gy/h). During the examination in the hospital, the patients were diagnosed with CRS. Within the framework of the bone marrow syndrome, deep thrombocytopenia, moderate leuko- and neutropenia, and moderate anemic syndrome were observed. The latter is not typical for the typical course of CRS and is a criterion indicating a subacute course of the disease. In addition, signs of chronic radiation dermatitis were found in the projection of the action of the ionizing radiation beam. After stopping the radiation exposure, the patients did not recover their hematopoietic function, and in the period of immediate consequences, they developed myelodysplastic syndrome (MDS) with further transformation into acute leukemia. Conclusion: 1. Accidental prolonged household or criminal contact with a source of ionizing radiation can lead to the formation of CRS with an atypical subacute course and the formation of MDS with transformation to acute leukemia in the outcome of the disease or in the period of its consequences. 2. It can be assumed that with external non-uniform radiation exposure, leading to the development of CRS and chronic radiation damage to the skin, agranulocytosis in the subacute course of CRS may be absent. 3. Adverse prognostic signs for the development of MDS and leukemia in the outcome or in the period of the consequences of subacute CRS with non-uniform exposure are long-lasting deep thrombocytopenia and anemic syndrome after the end of radiation exposure.

scholarly journals Influence of Age, Sex and Calendar Year on Lifetime Accumulated Red Bone Marrow Dose from Diagnostic Radiation Exposure

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e78027 ◽  
Author(s):  
Wolfgang Hoffmann ◽  
Merle Friederike Meiboom ◽  
Kerstin Weitmann ◽  
Claudia Terschüren ◽  
Heiner von Boetticher
Keyword(s):  
Bone Marrow ◽  
Radiation Exposure ◽  
Red Bone Marrow ◽  
Diagnostic Radiation ◽  
Diagnostic Radiation Exposure

Dosimetry with 188Re-labelled monoclonal anti-CD66 antibodies

2006 ◽  
Vol 45 (03) ◽  
pp. 134-138 ◽  
Author(s):  
T. Kull ◽  
N. M. Blumstein ◽  
D. Bunjes ◽  
B. Neumaier ◽  
A. K. Buck ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Gamma Camera ◽  
Absorbed Dose ◽  
Correlation Coefficients ◽  
Residence Times ◽  
Reliable Prediction ◽  
Red Bone Marrow ◽  
Antibody Preparation ◽  
Simplified Method

SummaryAim: For the therapeutic application of radiopharmaceuticals the activity is determined on an individual basis. Here we investigated the accuracy for a simplified assessment of the residence times for a 188Re-labelled anti-CD66 monoclonal antibody. Patients, methods: For 49 patients with high risk leukaemia (24 men, 25 women, age: 44 ± 12 years) the residence times were determined for the injected 188Re-labelled anti-CD66 antibodies (1.3 ± 0.4 GBq, 5–7 GBq/mg protein, >95% 188Re bound to the antibody) based on 5 measurements (1.5, 3, 20, 26, and 44 h p.i.) using planar conjugate view gamma camera images (complete method). In a simplified method the residence times were calculated based on a single measurement 3 h p.i. Results: The residence times for kidneys, liver, red bone marrow, spleen and remainder of body for the complete method were 0.4 ± 0.2 h, 1.9 ± 0.8 h, 7.8 ± 2.1 h, 0.6 ± 0.3 h and 8.6 ± 2.1 h, respectively. For all organs a linear correlation exists between the residence times of the complete method and the simplified method with the slopes (correlation coefficients R > 0.89) of 0.89, 0.99, 1.23, 1.13 and 1.09 for kidneys, liver, red bone marrow, spleen and remainder of body, respectively. Conclusion: The proposed approach allows reliable prediction of biokinetics of 188Re-labelled anti-CD66 monoclonal antibody biodistribution with a single study. Efficient pretherapeutic estimation of organ absorbed dose may be possible, provided that a more stable anti-CD66 antibody preparation is available.

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