scholarly journals Somatic shift to homozygosity for a chromosomal polymorphism in a child with acute lymphoblastic leukemia

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 350-353 ◽  
Author(s):  
J Stamberg ◽  
A Shende ◽  
P Lanzkowsky
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood ◽  
Clinical Remission ◽  
Wilms Tumor ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Polymorphism ◽  
Chromosome 15 ◽  
General Importance ◽  
Tetrasomy 8

Abstract A 12-year-old girl with acute lymphoblastic leukemia (ALL) had two types of acquired cytogenetic abnormalities in her pretreatment peripheral blood and bone marrow: hyperdiploidy due to tetrasomy 8, 10, and 21; and, in the hyperdiploid cells, a shift from heterozygosity to homozygosity for a polymorphic variant on chromosome 15. Both abnormalities disappeared after chemotherapy, when the patient entered clinical remission. It has recently been found that shifts to homozygosity occur in retinoblastoma and Wilms' tumor. Our observation extends this finding to leukemia and indicates that such shifts may have general importance in tumorigenesis.

scholarly journals Somatic shift to homozygosity for a chromosomal polymorphism in a child with acute lymphoblastic leukemia

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 350-353
Author(s):  
J Stamberg ◽  
A Shende ◽  
P Lanzkowsky
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood ◽  
Clinical Remission ◽  
Wilms Tumor ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Polymorphism ◽  
Chromosome 15 ◽  
General Importance ◽  
Tetrasomy 8

A 12-year-old girl with acute lymphoblastic leukemia (ALL) had two types of acquired cytogenetic abnormalities in her pretreatment peripheral blood and bone marrow: hyperdiploidy due to tetrasomy 8, 10, and 21; and, in the hyperdiploid cells, a shift from heterozygosity to homozygosity for a polymorphic variant on chromosome 15. Both abnormalities disappeared after chemotherapy, when the patient entered clinical remission. It has recently been found that shifts to homozygosity occur in retinoblastoma and Wilms' tumor. Our observation extends this finding to leukemia and indicates that such shifts may have general importance in tumorigenesis.

Comparison of minimal residual disease levels in bone marrow and peripheral blood in adult acute lymphoblastic leukemia

Leukemia ◽  
2019 ◽  
Vol 34 (4) ◽  
pp. 1154-1157 ◽  
Author(s):  
Michaela Kotrova ◽  
Antonia Volland ◽  
Britta Kehden ◽  
Heiko Trautmann ◽  
Matthias Ritgen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Minimal Residual

scholarly journals Prognostic significance of terminal transferase activity in childhood acute lymphoblastic leukemia: a prospective analysis of 164 patients

Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1267-1276 ◽  
Author(s):  
JJ Hutton ◽  
MS Coleman ◽  
S Moffitt ◽  
MF Greenwood ◽  
P Holland ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Central Nervous System Relapse ◽  
Transferase Activity

Abstract Whether the level of terminal deoxynucleotidyl transferase (TdT) activity in mononuclear cells from bone marrow and peripheral blood has prognostic significance has been analyzed prospectively in 164 children with T and non-T, non-B marked acute lymphoblastic leukemia (ALL). TdT was measured at diagnosis to assess its value as a predictor of duration of remission and length of survival. It was measured repeatedly during remission to assess whether it could predict relapse. Ninety-seven percent of the children achieved a complete remission of their disease, and 40% relapsed during the study. The level of TdT activity in blasts at diagnosis varied 1000-fold from patient to patient. There was no statistically significant relationship between TdT activity in cells at diagnosis and the achievement of complete remission, the duration of remission, or length of survival. TdT activity was significantly increased in the bone marrow of 65% of patients at the time of marrow morphological relapse, but was rarely increased in marrow from patients with isolated testicular or central nervous system relapse. Wide fluctuations in TdT activity were characteristically seen in mononuclear cells from the marrow and peripheral blood of patients with ALL at all stages of their disease. An isolated high value of TdT activity in the bone marrow or peripheral blood cannot be taken as evidence of impending relapse. Quantitative measurements of TdT activity alone on mononuclear cells from bone marrow and peripheral blood are helpful in differential diagnosis, but cannot guide therapy of children with ALL.

Status of Minimal Residual Disease Determines Outcome of Autologous HSCT in Adults with High-Risk Acute Lymphoblastic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2321-2321
Author(s):  
Sebastian Giebel ◽  
Beata Stella-Holowiecka ◽  
Malgorzata Krawczyk-Kulis ◽  
Nicola Goekbuget ◽  
Dieter Hoelzer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Minimal Residual

Abstract Abstract 2321 Poster Board II-298 The role of autologous hematopoietic stem cell transplantation (autoHSCT) in the treatment of adult acute lymphoblastic leukemia (ALL) is a subject of controversies as several prospective studies failed to prove its advantage over maintenance chemotherapy. Those studies, however, did not take into account the status of minimal residual disease (MRD), which is now recognized a potent predictor for relapse among patients treated with conventional-dose chemotherapy. The goal of this analysis was to determine the impact of MRD on outcome of autoHSCT. Data on 123 autoHSCT recipients collected from 6 study groups cooperating in the European Leukemia Net were analyzed. Median age of 77 B-lineage and 46 T-lineage high-risk ALL patients was 31 (16-59) years. Ph+ ALL was recognized in 20 cases. All patients were in first complete remission (CR) lasting 6 (1.5-22) months. Peripheral blood was used as a source of stem cells in 67 patients whereas bone marrow, in 56 cases. Conditioning was based on chemotherapy alone (n=76) or total body irradiation (n=47). MRD was evaluated in bone marrow with the use of either multiparametric flow cytometry (n=79) or molecular techniques (n=44). MRD level of 0.1% bone marrow cells was used as a cut-off point for the purpose of this study. At the time of autoHSCT MRD was &0.1% in 93 patients and ≧0.1% in 30 cases. With the median follow up of 5 years, the probability of leukemia-free survival (LFS) at 5 years for the whole group equaled 48% (+/-5). Three patients died of transplantation-related complications. The LFS rate was significantly higher for patients with the MRD level at transplantation &0.1% compared to those with MRD ≧0.1% (57% vs. 19%, p=0.0002). The difference was particularly pronounced for peripheral blood HSCT (66% vs. 20%, p=0.0006) and for T-lineage ALL (62% vs. 8%, p=0.001). In a multivariate analysis adjusted for other potential prognostic factors (age, CR duration, Ph+ ALL, immunophenotype, source of stem cells, type of conditioning), the MRD status &0.1% remained the only independent factor associated with increased LFS (HR=2.5, p=0.0009). CONCLUSIONS: MRD status is the most important predictor for LFS after autoHSCT in adults with ALL. More than half of patients with high risk disease and low MRD level at the time of transplantation may be cured. This observation may contribute to re-evaluation of the role of autoHSCT in the therapy of adult ALL. Disclosures: No relevant conflicts of interest to declare.

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 Relationship of genetic deviations with laboratory indicators of peripheral blood and bone marrow in children with acute lymphoblastic leukemia

2021 ◽  
Vol 25 (1(97)) ◽  
pp. 11-18
Author(s):  
O. Vynnytska ◽  
O. Dorosh ◽  
L. Dubey ◽  
N. Dubey
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Chromosomal Aberrations ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Translocation ◽  
Chromosomal Translocations ◽  
Laboratory Parameters

The aim of this study was to evaluate the prognostic value of the relationship between genetic abnormalities and clinical and laboratory parameters of peripheral blood and bone marrow in children with acute lymphoblastic leukemia (ALL). Material and methods. 105 children diagnosed with ALL were examined (average age 6 years). To detect chromosomal translocations AF4/MLL t(4; 11) (q23; p23), BCR/ABL t (9; 22) (q34; q11), E2A/PBX1 t (1; 19) (q23; p13) and TEL/AML t(12; 21) (q13; q22) the method of polymerase chain reaction with reverse transcription (RT-PCR) was applicated. PCR was performed with specific primers for the appropriate chromosomal aberrations. Detection of PCR products was performed by electrophoresis in 2% agarose gel. Determination of minimal residual disease (MRD) was performed by multiparameter flow cytofluorimetry using monoclonal antibodies. Results. Among patients, the incidence of ALL is most pronounced in children aged 3 to 6 years - 37 people (35.2%) and aged 6 to 9 years - 26 people (24.8%). The highest accidence was found among patients with chromosomal translocation TEL/AML - 22 (21%) of patients with a median age of 5 years. In the second place, the frequency of mutations is the translocation of E2A / PBX1. BCR / ABL translocation was less common - 1.9% of patients, but the expression of this gene indicates a bad course of the disease, as patients after cytostatic therapy under the ALLIC BFM 2009 program had a recurrence. Recurrence has also been observed in patients with TEL/AML chromosomal translocation. Determination of MRD showed its increased level in patients with chromosomal aberrations BCR / ABL and TEL/AML throughout the treatment phase. In addition, patients in these groups were diagnosed with initial leukocytosis followed by leukopenia after a course of chemotherapy. Patients of all groups showed a decrease in hemoglobin. Conclusion. The most significant changes in clinical and laboratory parameters were found among patients with chromosomal translocations BCR/ABL and TEL/AML, as evidenced by the development of relapses in patients of these groups. The low level of association between karyotype disorders, with the formation of AF4/MLL and E2A/PBX1, and clinical and laboratory parameters in patients with GLL may indicate that the isolated clonal disorders are independent prognostic factors for the course of the disease.

CXCR4 Antagonists Mobilize Acute Lymphoblastic Leukemia Cells into the Peripheral Blood and Inhibit Engraftment in Mice.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4592-4592
Author(s):  
Julius Juarez ◽  
John Hewson ◽  
Adam Cisterne ◽  
Rana Baraz ◽  
Kenneth F. Bradstock ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Cxcr4 Antagonists

Abstract The role of CXCL12 in the growth of B cell progenitor acute lymphoblastic leukemia (ALL) and the homing of these cells to the bone marrow has been well established. However the effect of modulating CXCL12/CXCR4 interactions on the growth of ALL cells in vivo has not been examined. In this study we used specific peptide and small molecule antagonists of CXCR4 to examine the importance of CXCL12/CXCR4 interactions in the development of leukemia in an in-vivo murine model of ALL. CXCR4 antagonists induced mobilization of human and murine B cell progenitor ALL cells into the peripheral blood, with a 3.8±1.9 and 6.5±3.3 fold increase in leukemic cells/ml one hour after administration of the antagonist respectively, similar to that observed for normal progenitors. Daily administration of AMD3100 commencing the day following the injection of cells and continuing for 21 days resulted in a mean reduction in peripheral blood white cell count of 50±12% and the leukemic cell count of 63±4%. There was also a significant reduction in both the total cells in the spleen of 58±1% and the leukemic cell number in this organ of 75±11%. A significant reduction in leukemic cell numbers in the bone marrow was observed in one (44% reduction) case. There was reduced infiltration of other organs including kidney, liver and skeletal muscle. This study demonstrates that disrupting the CXCL12/CXCR4 axis in B cell progenitor ALL reduces the tumor burden. Whether this is due to direct inhibitory effects on proliferation and survival, or results from disruption of the leukemic cell interactions within the bone marrow remains to be determined.

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