Hyperdiploid Acute Lymphoblastic Leukemia With 51 to 65 Chromosomes: A Distinct Biological Entity With a Marked Propensity to Undergo Apoptosis

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 315-320 ◽  
Author(s):  
Chikako Ito ◽  
Masa-aki Kumagai ◽  
Atsushi Manabe ◽  
Elaine Coustan-Smith ◽  
Susana C. Raimondi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Interleukin 1 ◽  
Flow Cytometric Analysis ◽  
Growth Potential ◽  
Leukemic Cells ◽  
Biological Entity ◽  
Allogeneic Bone ◽  
Cell Recovery ◽  
Flow Cytometric

To determine the cellular basis for the excellent clinical outcome of hyperdiploid acute lymphoblastic leukemia (ALL), defined by a modal chromosome number of 51 to 65, we assessed the growth potential of leukemic cells from 129 children with newly diagnosed ALL. Flow cytometric analysis was used to compare leukemic cell recoveries at the beginning and at the end of 7-day cultures on allogeneic bone marrow–derived stromal layers. The median percentage of cell recovery after culture was 91% (range, <1% to 550%). Among the 25 hyperdiploid cases, only two had cell recoveries above the median value, compared with 63 of 104 cases with different ploidies (P< .001); 21 had recoveries within the first quartile, in contrast to only 12 of the 104 other cases. Cell recoveries in the 16 cases with duplications of chromosomes 4 and 10, a feature previously associated with a superior outcome, were all within the first quartile. Flow cytometric studies indicated that rapid induction of apoptosis was the underlying cause of low cell recoveries in cases with hyperdiploidy. The demise of hyperdiploid cells on stroma was not due to failure to adhere with stromal elements (as shown by electron microscopy) or to deficiencies of interleukin-1 (IL-1), IL-2, IL-3, IL-4, IL-6, IL-7, IL-11, stem-cell factor, interferon- (IFN-), tumor necrosis factor- (TNF-), or to combinations of these cytokines. Inactivation of IL-4, IFN- and TNF-, which if secreted by stromal layers could be toxic to ALL cells, failed to improve the survival of hyperdiploid blasts. We conclude that leukemic cells bearing 51 to 65 chromosomes have a marked propensity to undergo apoptosis. The stringent survival requirements of these cells, together with their potentially higher sensitivity to antileukemic drugs, may well account for the high cure rates achieved in patients with this form of ALL.

Hyperdiploid Acute Lymphoblastic Leukemia With 51 to 65 Chromosomes: A Distinct Biological Entity With a Marked Propensity to Undergo Apoptosis

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 315-320 ◽  
Author(s):  
Chikako Ito ◽  
Masa-aki Kumagai ◽  
Atsushi Manabe ◽  
Elaine Coustan-Smith ◽  
Susana C. Raimondi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Interleukin 1 ◽  
Flow Cytometric Analysis ◽  
Growth Potential ◽  
Leukemic Cells ◽  
Biological Entity ◽  
Allogeneic Bone ◽  
Cell Recovery ◽  
Flow Cytometric

Abstract To determine the cellular basis for the excellent clinical outcome of hyperdiploid acute lymphoblastic leukemia (ALL), defined by a modal chromosome number of 51 to 65, we assessed the growth potential of leukemic cells from 129 children with newly diagnosed ALL. Flow cytometric analysis was used to compare leukemic cell recoveries at the beginning and at the end of 7-day cultures on allogeneic bone marrow–derived stromal layers. The median percentage of cell recovery after culture was 91% (range, &lt;1% to 550%). Among the 25 hyperdiploid cases, only two had cell recoveries above the median value, compared with 63 of 104 cases with different ploidies (P&lt; .001); 21 had recoveries within the first quartile, in contrast to only 12 of the 104 other cases. Cell recoveries in the 16 cases with duplications of chromosomes 4 and 10, a feature previously associated with a superior outcome, were all within the first quartile. Flow cytometric studies indicated that rapid induction of apoptosis was the underlying cause of low cell recoveries in cases with hyperdiploidy. The demise of hyperdiploid cells on stroma was not due to failure to adhere with stromal elements (as shown by electron microscopy) or to deficiencies of interleukin-1 (IL-1), IL-2, IL-3, IL-4, IL-6, IL-7, IL-11, stem-cell factor, interferon- (IFN-), tumor necrosis factor- (TNF-), or to combinations of these cytokines. Inactivation of IL-4, IFN- and TNF-, which if secreted by stromal layers could be toxic to ALL cells, failed to improve the survival of hyperdiploid blasts. We conclude that leukemic cells bearing 51 to 65 chromosomes have a marked propensity to undergo apoptosis. The stringent survival requirements of these cells, together with their potentially higher sensitivity to antileukemic drugs, may well account for the high cure rates achieved in patients with this form of ALL.

scholarly journals γδ T-Cell Acute Lymphoblastic Leukemia/Lymphoma: Discussion of Two Pediatric Cases and Its Distinction from Other Mature γδ T-Cell Malignancies

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Eric X. Wei ◽  
Vasiliki Leventaki ◽  
John K. Choi ◽  
Susana C. Raimondi ◽  
Elizabeth M. Azzato ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
White Cell Count ◽  
Flow Cytometric Analysis ◽  
Molecular Diagnostic ◽  
Allogeneic Bone ◽  
Γδ T Cell ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Cellular Markers

Gamma delta (γδ) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Here we report two pediatric T-ALL cases and present their clinical features, histology, immunophenotypes, cytogenetics, and molecular diagnostic findings. The first patient is a two-year-old girl with leukocytosis, circulating lymphoblasts, and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23 resulting in an MLL and AF10 fusion transcript, which may be the first reported in γδ T-ALL. She responded to the chemotherapy protocol poorly and had persistent diseases. Following an allogeneic bone marrow transplant, she went into remission. The second patient is an eleven-year-old boy with a normal white cell count, circulating blasts, and a normal karyotype, but without any immature cellular markers by flow cytometric analysis. He responded to the chemotherapy well and achieved a complete remission. These cases demonstrate the diverse phenotypic, cytogenetic, and molecular aspects of γδ T-ALL. Early T-precursor- (ETP-) ALL and their differential diagnosis from other mature γδ T-cell leukemia/lymphomas are also discussed.

scholarly journals Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid less than 45 line

Blood ◽  
1990 ◽  
Vol 75 (5) ◽  
pp. 1170-1177
Author(s):  
CH Pui ◽  
AJ Carroll ◽  
SC Raimondi ◽  
VJ Land ◽  
WM Crist ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Sex Chromosomes ◽  
Chromosomal Abnormalities ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Chromosome 21 ◽  
Leukemic Cells ◽  
Karyotypic Analysis ◽  
Flow Cytometric ◽  
Poor Treatment

Cytogenetic and DNA flow cytometric analyses of leukemic cells from 2,184 children with newly diagnosed acute lymphoblastic leukemia (ALL) identified 27 cases (1.2%) that had a hypodiploid line with fewer than 45 chromosomes per cell. Had cytogenetic techniques been used alone, seven cases would have been missed, compared with five if only flow cytometry had been used. For comparative purposes, the 27 cases were divided into three groups: near-haploid (n = 10), hypodiploid 30–40 (n = 9), and hypodiploid 41–44 (n = 8). Blast cells from patients with near-haploid ALL lacked structural chromosomal abnormalities; showed nonrandom retention of two copies of chromosomes 8, 10, 14, 18, 21, and the sex chromosomes; and had a second leukemic line with exactly twice the number of chromosomes or DNA content. Karyotypic analysis of the hypodiploid 30–40 and hypodiploid 41–44 groups disclosed structural abnormalities in the stemline or sideline of most of the well-banded cases; those in the latter group were similar to findings in cases with 45 chromosomes. As in the near-haploid group, chromosome 21 and the sex chromosomes were preferentially retained in the hypodiploid 30–40 and 41–44 cases. Except for a slight excess of female patients in the near- haploid group and an older age at diagnosis in the hypodiploid 30–40 cases, there were no initial clinical features that distinguished these patients from the general ALL population. Despite intensive treatment and short follow-up, 17 of the 27 patients have relapsed. This study suggests that the poor treatment responsiveness of hypodiploid ALL is not limited to the more than 80% of the patients who have 45 chromosomes per leukemic cell and demonstrates that cytogenetic and flow cytometric analyses are complementary in the evaluation of children with ALL.

Flow cytometric analysis of expression of interleukin-2 receptor beta chain (p70-75) on various leukemic cells

Blood ◽  
1990 ◽  
Vol 76 (4) ◽  
pp. 767-774 ◽  
Author(s):  
S Hoshino ◽  
K Oshimi ◽  
M Tsudo ◽  
M Miyasaka ◽  
M Teramura ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Flow Cytometric Analysis ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Beta Chain ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Flow Cytometric

Abstract We analyzed the expression of the interleukin-2 receptor (IL-2R) beta chain (p70–75) on various leukemic cells from 44 patients by flow cytometric analysis using the IL-2R beta chain-specific monoclonal antibody (MoAb), designated Mik-beta 1, which has been recently developed. Flow cytometric analysis demonstrated the expression of the IL-2R beta chain on granular lymphocytes (GLs) from all eight patients with granular lymphocyte proliferative disorders (GLPDs), on adult T- cell leukemia (ATL) cells from all three patients with ATL, and on T- cell acute lymphoblastic leukemia (T-ALL) cells from one of three patients with T-ALL. Although GLs from all the GLPD patients expressed the IL-2R beta chain alone and not the IL-2R alpha chain (Tac-antigen: p55), ATL and T-ALL cells expressing the beta chain coexpressed the alpha chain. In two of seven patients with common ALL (cALL) and in both patients with B-cell chronic lymphocytic leukemia, the leukemic cells expressed the alpha chain alone. Neither the alpha chain nor the beta chain was expressed on leukemic cells from the remaining 28 patients, including all 18 patients with acute nonlymphocytic leukemia, five of seven patients with cALL, all three patients with multiple myeloma, and two of three patients with T-ALL. These results indicate that three different forms of IL-2R chain expression exist on leukemic cells: the alpha chain alone; the beta chain alone; and both the alpha and beta chains. To examine whether the results obtained by flow cytometric analysis actually reflect functional aspects of the expressed IL-2Rs, we studied the specific binding of 125I-labeled IL-2 (125I-IL-2) to leukemic cells in 18 of the 44 patients. In addition, we performed 125I-IL-2 crosslinking studies in seven patients. The results of IL-2R expression of both 125I-IL-2 binding assay and crosslinking studies were in agreement with those obtained by flow cytometric analysis. These results indicate that flow cytometric analysis using MoAbs, anti-Tac, and Mik-beta 1 is useful for detecting the expression of the IL-2R chains.

scholarly journals Near-haploid acute lymphoblastic leukemia: a unique subgroup with a poor prognosis?

Blood ◽  
1981 ◽  
Vol 58 (1) ◽  
pp. 14-19 ◽  
Author(s):  
GM Brodeur ◽  
DL Williams ◽  
AT Look ◽  
WP Bowman ◽  
DK Kalwinsky
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Dna Content ◽  
Poor Prognosis ◽  
Lymphoblastic Leukemia ◽  
Periodic Acid ◽  
Flow Cytometric Analysis ◽  
Chromosome 21 ◽  
Periodic Acid Schiff ◽  
Flow Cytometric ◽  
Block Pattern

We describe two adolescent girls with acute lymphoblastic leukemia (ALL) whose leukemia cells were near-haploid. Their lymphoblasts stained in a block pattern with periodic acid Schiff and had “common ALL” surface markers confirmed by indirect immunofluorescence. Each patient had two populations of blasts, one near-haploid and one hyperdiploid, which was an exact doubling of the near-haploid karyotype. The first patient had a predominant population of cells with 26 chromosomes and a few with 52, while the second had a predominance of cells with 56 and a minority with 28. Flow cytometric analysis of DNA content initially detected the minor near-haploid population in the second patient, which was confirmed later by cytogenetic review of the marrow sample. In addition to our two patients, only four patients have been reported with near-haploid ALL. Of these six, five were girls, five were adolescents, and five had short survivals (median, 10 mo). All six had disomy of chromosome 21 with or without disomy for chromosomes 10, 14, 18, or X (four patients each). Thus, near-haploid ALL may represent a unique subgroup of ALL with a poor prognosis. To detect these and other possible subgroups, we have included cytogenetic analysis and flow cytometric analysis of DNA content in our initial evaluation of patients with ALL.

Use of Four-Color Flow Cytometric Assay for Discrimination of Hematogone from Lymphoblast: Critical Issue for MRD Assessment in B-ALL Patients

2020 ◽  
Author(s):  
Mehdi Allahbakhshian Farsani ◽  
Esmaeil Shahabi Satlsar ◽  
Alireza Mohseni ◽  
Mohammad Mosleh ◽  
Mahdieh Mehrpouri ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Critical Issue ◽  
Color Flow ◽  
Flow Cytometric ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Cells

Background: Hematogones are normal B-cell precursor which can be seen in different physiological and pathological conditions. Due to variation in B-cell acute lymphoblastic leukemia (B-ALL) blasts immunophenotyping and interference of hematogones in minimal residual disease (MRD) assessment, precise discrimination of hematogones is very crucial.  The purpose of this study was to evaluate the expression pattern of surface markers in hematogones and compare them with lymphoblasts. Material and Methods: In this applied study, flow cytometric analysis was performed using Coulter FC-500 and MXP software in 4-color combination and 6 different tubes. In this study, 85 patients diagnosed with acute lymphoblastic leukemia were evaluated. Out of these patients, 45 were boys and 40 were girls. Patients aged from 1 to 15 years old. In addition, 27 bone marrow samples from other patients aged 4 to 18 years were included in this investigation. These samples had been obtained for other diagnostic purposes, such as immune thrombocytopenic purpura and juvenile idiopathic arthritis. Results: During flow cytometric analysis, hematogones showed expressions of CD19, CD20, CD22, CD10, CD45, CD81, CD123, CD9, CD34 (partial expression), and tdt (partial expression). In these patients, hematgones were negative for CD66c expression. Lymphoblastic cells were positive for CD19, CD20 (in some cases), CD22, CD10, CD45, CD81, CD123, CD58, CD9, CD66c, CD34 (in most cases), and TDT. CD81 mean fluorescence intensity (MFI) in hematogones was higher than that in lymphoblasts. (112.5 (30-251) vs. 17.5 (5-30); P<0.0001) Conclusion: According to findings of this study, it seems that the use of CD81, CD58, CD123, CD66c, CD9, and CD81 MFI in combination with B-Cells associated markers can be very effective in differentiating hematogone from lymphoblast.

scholarly journals Near-haploid acute lymphoblastic leukemia: a unique subgroup with a poor prognosis?

Blood ◽  
1981 ◽  
Vol 58 (1) ◽  
pp. 14-19 ◽  
Author(s):  
GM Brodeur ◽  
DL Williams ◽  
AT Look ◽  
WP Bowman ◽  
DK Kalwinsky
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Dna Content ◽  
Poor Prognosis ◽  
Lymphoblastic Leukemia ◽  
Periodic Acid ◽  
Flow Cytometric Analysis ◽  
Chromosome 21 ◽  
Periodic Acid Schiff ◽  
Flow Cytometric ◽  
Block Pattern

Abstract We describe two adolescent girls with acute lymphoblastic leukemia (ALL) whose leukemia cells were near-haploid. Their lymphoblasts stained in a block pattern with periodic acid Schiff and had “common ALL” surface markers confirmed by indirect immunofluorescence. Each patient had two populations of blasts, one near-haploid and one hyperdiploid, which was an exact doubling of the near-haploid karyotype. The first patient had a predominant population of cells with 26 chromosomes and a few with 52, while the second had a predominance of cells with 56 and a minority with 28. Flow cytometric analysis of DNA content initially detected the minor near-haploid population in the second patient, which was confirmed later by cytogenetic review of the marrow sample. In addition to our two patients, only four patients have been reported with near-haploid ALL. Of these six, five were girls, five were adolescents, and five had short survivals (median, 10 mo). All six had disomy of chromosome 21 with or without disomy for chromosomes 10, 14, 18, or X (four patients each). Thus, near-haploid ALL may represent a unique subgroup of ALL with a poor prognosis. To detect these and other possible subgroups, we have included cytogenetic analysis and flow cytometric analysis of DNA content in our initial evaluation of patients with ALL.

Comment on: Value of flow cytometric analysis of peripheral blood samples in children diagnosed with acute lymphoblastic leukemia

2017 ◽  
Vol 65 (2) ◽  
pp. e26845
Author(s):  
Ryan J. Summers ◽  
L. Katie Metrock ◽  
Sunita Park ◽  
Scott Gillespie ◽  
Sharon Castellino ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Blood Samples ◽  
Flow Cytometric
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