The monitoring of acute leukemia patients: Part 1. Basic morphometric characteristics of bone marrow blast cells in acute lymphoblastic leukemia

1990 ◽  
Vol 14 (9) ◽  
pp. 795-800 ◽  
Author(s):  
V.M. Pogorelov ◽  
E.N. Timkina ◽  
G. Mattes ◽  
R. Ile ◽  
G. Yu. Miterev ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Morphometric Characteristics ◽  
Bone Marrow Blast ◽  
Blast Cells

Molecular Genetic Characterization of 3'-Deletion of MLL Gene in Infant Acute Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2498-2498
Author(s):  
Grigory Tsaur ◽  
Olga Plekhanova ◽  
Alexander Popov ◽  
Tatyana Gindina ◽  
Yulia Olshanskaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Fish Analysis ◽  
Long Distance ◽  
Mll Gene ◽  
Partner Gene ◽  
Genetic Features ◽  
Blast Cells

Abstract Abstract 2498 Background. MLL gene rearrangements are associated with unfavorable outcome in infant acute lymphoblastic leukemia (ALL) and have intermediate prognosis in infant acute myeloid leukemia (AML). Application of fluorescence in-situ hybridization (FISH) allows detecting not only conventional MLL rearrangements, but also concurrent 3'-deletion of MLL gene. However, detailed characteristics of infant leukemia carrying 3' MLL deletion remain unclear. Aim. To investigate molecular genetic features of MLL-rearranged infant acute leukemia with concurrent 3' MLL deletion. Methods. 64 patients (27 boys and 37 girls) aged from 1 day to 11 months (median 6.6 months) including 44 ALL patients, 18 AML patients, 1 patient with acute bilineage leukemia and 1 patient with acute undifferentiated leukemia were enrolled in the current study. Chromosome banding analysis was done according to standard procedure. FISH analysis using LSI MLL Dual Color, Break Apart Rearrangement Probe (Abbott Molecular, USA) was performed on at least 200 interphase nuclei and on all available metaphases. Presence of MLL rearrangements was detected by FISH, reverse-transcriptase PCR. In 29 cases long-distance inverse PCR was additionally performed. In case of MLL rearrangement presence standard FISH pattern was defined as simultaneous detection of 3 different fluorescent signals: 1 fused (orange) signal, 1 green signal derived from 3' part of MLL gene, 1 red signal from 5' end of MLL (1F1G1R). MLL rearrangements with concurrent 3' MLL deletion led to 1F1R FISH pattern formation due to lack of green signal. Results. FISH revealed MLL rearrangements in 73% of ALL cases that was higher than frequency of 11q23 translocations detected by conventional cytogenetics — 55%. In MLL-positive cases we found 38 patients (81%) with standard FISH pattern, 7 ones (15%) with concurrent 3'-deletion of MLL gene and 2 (4%) with complex MLL rearrangements. Among patients with 3' MLL deletions there were 1 case with 5' MLL duplication (1F2R) and 1 case with 5' MLL triplication (1F3R). Frequency of 3'-deletions were similar in ALL and AML patients (13% and 15%, respectively). We did not find more than one FISH pattern in bone marrow blast cells of each patient with 3' MLL deletion. In this cohort of patients all blast cells carried concurrent 3'-deletion of MLL gene. Moreover, percentage of blast cells carrying MLL rearrangements did not differ significantly between patients with standard FISH pattern (median 97%, range 22–100%) and 3'-deletion (median 83%, range 13–99%) (p=0.206). 3'-deletion of MLL was not associated with breakpoint position in MLL gene and type of translocation partner gene. MLL translocation partner genes detected in patients with 3' deletions were as follows AF4(n=2), MLLT3(n= 3), MLLT10(n=2). None of the patients with 3'-deletions had reciprocal fusion gene. Initial patients' characteristics (age, sex, WBC count, immunophenotype, CNS-status, type of MLL partner gene) and treatment response parameters (day 8 peripheral blood blast cell count, day 15 bone marrow status, day 36 remission achievement, minimal residual disease status at time point 4) did not differ significantly between 2 groups. Although cumulative incidence of relapse was lower in patients with 3'-deletion as compared to patients with standard FISH pattern (0.31±0.04 and 0.55±0.01, respectively), difference between these two groups was not statistically significant (p=0.359). Conclusion. In our work we characterized rare subgroup of infant MLL-rearranged acute leukemia carrying concurrent 3' MLL deletion. Our data provide additional information of molecular genetic features of acute leukemia in children younger than one year. 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 Cytokinetic parameters of erythropoiesis under normal health conditions and during the development of acute lymphoblastic and acute myeloblastic leukemia

2021 ◽  
Vol 30 ◽  
pp. 04007
Author(s):  
Evgeniy Seliverstov ◽  
Marina Skorkina
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Scientific Research ◽  
Acute Myeloblastic Leukemia ◽  
Health Conditions ◽  
Immature Cells ◽  
Normal Health ◽  
Hematopoietic Activity

The article presents the application of the method for determining the quantitative parameters of erythropoiesis to patients with acute leukemia. The objective of the work is an investigation of erythropoiesis cytokinetic parameters under the normal health conditions and during the development of the acute lymphoblastic leukemia and the acute myeloblastic leukemia. It was found that the distribution of reticulocytes shifts towards an increase of immature reticulocyte fraction while the ratio between maturing and immature cells remains unchanged. The method presented can be used in clinical diagnostic and scientific research of bone marrow hematopoietic activity.

scholarly journals Acute leukemia with Burkitt's tumor cells: A study of six cases with special reference to lymphocyte surface markers

Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 183-188 ◽  
Author(s):  
G Flandrin ◽  
JC Brouet ◽  
MT Daniel ◽  
JL Preud'homme
Keyword(s):  
Electron Microscopy ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Tumor Cells ◽  
Lymphoblastic Leukemia ◽  
Surface Markers ◽  
Lymphocyte Surface Markers ◽  
Surface Immunoglobulins ◽  
Blast Cells

Abstract In six patients with acute leukemia (about 2% of the patients referred for acute lymphoblastic leukemia) the blast cells invading bone marrow and blood showed all the cytologic, cytochemical, and electron microscopy features of Burkitt's tumor cells. The presence of monoclonal surface immunoglobulins (their synthesis being proved by in vitro culture experiments), the binding of IgG aggregates, and the absence of rosette formation with sheep red cells documented the monoclonal B-cell origin of these blast cells which is in sharp contrast to the findings in common acute lymphoblastic leukemia. The course of the disease was usually rapidly fatal without chemotherapy- induced remission.

Improved Outcome With T-Cell–Depleted Bone Marrow Transplantation for Acute Leukemia

1999 ◽  
Vol 17 (5) ◽  
pp. 1545-1545 ◽  
Author(s):  
Franco Aversa ◽  
Adelmo Terenzi ◽  
Alessandra Carotti ◽  
Rita Felicini ◽  
Roberta Jacucci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Antithymocyte Globulin ◽  
Lymphoblastic Leukemia ◽  
Acute Myeloid

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell–depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell–depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.

scholarly journals Immunophenotypic Profile of Blast Cells as a Marker for Diagnosis of Relapsed Children Acute Lymphoblastic Leukemia

2021 ◽  
Vol 6 (1) ◽  
pp. 56-64
Author(s):  
O. A. Vynnytska ◽  
◽  
O. I. Dorosh ◽  
L. Ya. Dubey ◽  
N. V. Dubey
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Translocation ◽  
Cytostatic Therapy ◽  
Blast Cells ◽  
Minimal Residual

Immunophenotyping of leukemia cells was studied in this work; minimal residual disease was monitored among children with acute lymphoblastic leukemia under conditions of relapse and complete remission after the application of ALLIC-BFM 2009 cytostatic therapy. The study showed that after application of ALLIC-BFM 2009 therapy, 88% of children had complete remission, and 12% had relapses. Among patients with relapses, the number of blast cells in the bone marrow was at a high level (more than 6%). Monitoring of patients during therapy established an increase in the minimal residual disease level of more than 1% after treatment in patients with recurrent disease. Immunophenotyping of blast cells among patients with relapse showed the expression of linear independent antigens HLA (93%), Auti-TdT (91%), CD10 (78%), CD38 (91%) and CD34 (57%) and B-linear antigens: CD19, CD22, CD58, CD79a, the highest expression was found for the CD19 antigen. A low level of expression of CD45 (28%) was recorded with relapses of acute lymphoblastic leukemia and high (89%) level was with complete remission of the disease. We did not detect expression of antigens characteristic of T-cell acute lymphoblastic leukemia in bone marrow of patients with acute lymphoblastic leukemia, both with relapses and with remission. At the same time, the expression of myeloid antigens (CD33 and CD13) was noted among acute lymphoblastic leukemia patients. Among patients, the incidence of acute lymphoblastic leukemia was the most pronounced in children aged from 3 to 6 years – 37 patients (35.2%) and aged from 6 to 9 years – 26 (24.8%) patients. The highest accidence was found among patients with chromosomal translocation TEL / AML – 22 (21%) patients with a median age 5 years. In second place, the frequency of mutations is the translocation of E2A / PBX1. BCR / ABL translocation was less common. It was noted in 1.9% of patients, but the expression of this gene indicated a bad course of the disease, as patients after cytostatic therapy under the ALLIC BFM 2009 program had a recurrence. Recurrence was also observed in patients with TEL/AML chromosomal translocation. Determination of minimal residual disease 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. The biggest changes in clinical and laboratory parameters were found between 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 acute lymphoblastic leukemia may indicate that the isolated clonal disorders are independent prognostic factors for the course of the disease

Comparative analysis of chromosomal aberrations in children with acute leukemia

2020 ◽  
Vol 5-6 (215-216) ◽  
pp. 7-14
Author(s):  
Zhansaya Nessipbayeva ◽  
◽  
Minira Bulegenova ◽  
Meruert Karazhanova ◽  
Dina Nurpisova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Chromosomal Aberrations ◽  
Cytogenetic Study ◽  
Normal Karyotype ◽  
Blast Cell ◽  
Bone Marrow Blast ◽  
Scientific Center ◽  
Blast Cells ◽  
Medical Histories

Leukemia is a hematopoetic tissue tumor with a primary lesion of the bone marrow, where the morphological substrate is the blast cell. Chromosomal and molecular genetic aberrations play a major role in the acute leukemia pathogenesis, determing the morphological, immunological and clinical features of the disease. Our study was aimed to to analyze retrospectively the structure and frequency of chromosomal aberrations in children with initially diagnosed acute leukemia. Material and methods. Medical histories retrospective analysis of children charged to oncohematology department of the «Scientific Center of Pediatrics and Pediatric Surgery» in Almaty for the period 2015 - 2017 was carried out. 310 histories with primary diagnosed acute leukemia were studied. Results and discussion. Among 310 patients different chromosome aberrations were isolated in 158 patients (51%) during cytogenetic and molecular cytogenetic (in situ hybridization) studies of bone marrow blast cells. A normal karyotype was observed in 102 patients (33%). Conclusion. The lymphoblastic variant of acute leukemia was determined in 75.5%, that indicates its leading role in AL structure among the children of different ages. AML was determined in 22.6% of all OL cases. The most frequent chromosomal rearrangement in ALL patients was blast cell chromosome hyperdiploidy (10,6%) and t(12;21)(p13;q22)/ETV6-RUNX1,which was detected in 37 (16%) patients. The most frequent AML abberation was t (8;21) (q22;q22)/RUNX1-RUNX1T1, identified in 15 (21.4%) patients. Keywords: acute leukemia, bone marrow, blast cells, karyotype, chromosomal aberrations, cytogenetic study.

The Usefulness of CD71 Expression by Flow Cytometry in the Diagnosis of Acute Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2533-2533 ◽  
Author(s):  
Qian Liu ◽  
Mangju Wang ◽  
Yang Hu ◽  
Haizhou Xing ◽  
Xue Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Clonal Evolution ◽  
Expression Level ◽  
Leukemic Cells ◽  
Bone Marrow Blast ◽  
Blast Cells ◽  
The Mean ◽  
Acute Megakaryocytic Leukemia ◽  
Normal Controls

Abstract Abstract 2533 CD71 (transferring receptor 1) is an integral membrane glycoprotein that plays an important role in cellular uptake of iron. It is well known as a marker for cell proliferation and activation. Although all proliferating cells in hematopoietic system express CD71, however, CD71 has been considered as a useful erythroid-associated antigen. The expression proportion on nucleated red blood cells was significantly higher than other cells, approximately 80% of all CD71 positive cells were of CD71 positive erythroid cells in normal bone marrow. CD71 was usually considered as the representative marker for differentiating erythroblasts and diagnosing acute erythroid leukemia (AEL) by flow cytometry. At the ISAC 2000 Congress, most experts agreed that at least one or more B, T, myeloid, erythroid and megakaryocytic reagents should be included in the essential panel. The reagents recommended for erythroid cells included CD36, CD71 and glycophorin A (GlyA). However, there was no agreement on how to choose and group these antibodies. In the practical analysis of immune phenotypes of leukemic cells we noted that no CD71 expression was detected on blasts of some cases of AEL with typical morphological and cytochemical findings, but other types of acute myeloblastic leukemia (AML) cells may express CD71. Thus, we speculated that CD71 expression may associate with the abnormal antigen expression resulting from hematopoietic disorders. In this study, we evaluated CD71 expression on different acute leukemia cells in association with a variety of other antibodies. In this study we aimed to define CD71 as a flow cytometric marker for the diagnosis of acute leukemia. Bone marrow samples were collected from 82 newly diagnosed acute leukemia patients as well as 13 normal controls. The diagnosis were made according to the WHO 2008 diagnostic criteria. All 6 cases of AEL were erythroid/myeloid subtype (acute erythroid/myeloid leukemia, M6a). The samples were then analyzed using a four-color flow cytometer with antibody panels against a variety of lymphoid, myelomonocytic, erythroid and megakaryocytic antigens. The antibodies included anti-CD3, CD7, CD10, CD11b, CD13, CD14, CD15, CD16, CD19, CD20, CD33, CD34, CD45, CD56, CD61, CD64, CD71, CD117, GlyA, HLA-DR, IgG, IgM, MPO. Subpopulations of bone marrow cells were gated based on CD45 intensities and side scatter (SSC) value to further analyze the expression of antigens in different cell populations. Positive CD71 expression were identified on bone marrow blast cells of 41 (50%) acute leukemia patients and 9 (69.23%) normal controls. The mean expression level on normal controls was 35.99±19.06%. The mean CD71 expression level on blasts of AML with blasts differentiation at early stage of myelopoiesis (including FAB-M0/M1/M2/M4) was significantly higher than AML with partial differentiation of leukemic cells (FAB-M3/M5) and acuteB lymphoblastic leukemia (B-ALL) (p<0.05), with the mean expression level of 38.78±26.65%, 13.25±8.75% and 10.12±11.65%, respectively, and the latter two lower than normal controls (p<0.05). The percentage of CD71 expression level on blasts of acute megakaryocytic leukemia (FAB-M7) was 80.16±8.23%, significantly higher than normal controls, partial differentiation of leukemic cells (FAB-M3/M5), and B-ALL (p<0.05). The percentage of CD71 expression level on blasts of mixed lineage leukemia was 49.66±22.69%, significantly higher than B-ALL (p<0.05). Positive CD71 expression was found on bone marrow blast cells of 4 (66.67%) AEL cases, with the mean level percentage of 25.68±11.63% that was significantly lower than acute megakaryocytic leukemia (FAB-M7) (p<0.05) and was indifferent from normal controls and other types of acute leukemia. Using CD71 expression levels, we identified different abnormal cell clones simultaneously existing within bone marrow of 2 patients of AML with maturation (FAB-M2) and AEL, implicating the clonal evolution process from normal blasts to leukemic cells. CD71 is an important marker for diagnosing acute leukemia, and is useful for distinguishing the differentiation stages of AML. However, CD71 may not be the specific diagnostic marker for AEL. CD71 is also valuable for the observation of clonal evolution process of acute leukemia, which may be informative to the etiology of leukemia. Disclosures: No relevant conflicts of interest to declare.

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