scholarly journals Common ALL with pre-B-cell features showing (8;14) and (14;18) chromosome translocations

Blood ◽  
1983 ◽  
Vol 62 (5) ◽  
pp. 1142-1146 ◽  
Author(s):  
GJ Mufti ◽  
TJ Hamblin ◽  
DG Oscier ◽  
S Johnson
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Karyotype Analysis ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Chromosome Translocations ◽  
Blast Cells ◽  
Inguinal Lymphadenopathy

A 21-yr-old man presented with inguinal lymphadenopathy and splenomegaly. The peripheral blood showed a high blast cell count. The morphological and immunologic features of the blast cells were consistent with the diagnosis of common acute lymphoblastic leukemia (ALL) with 15% pre-B-cells. Banded karyotype analysis of the blood and the marrow cells, using the technique of methotrexate synchronization, revealed the presence of (8;14) and (14;18) chromosome translocations, a finding that has not been previously documented. The significance of these findings is discussed.

scholarly journals Common ALL with pre-B-cell features showing (8;14) and (14;18) chromosome translocations

Blood ◽  
1983 ◽  
Vol 62 (5) ◽  
pp. 1142-1146 ◽  
Author(s):  
GJ Mufti ◽  
TJ Hamblin ◽  
DG Oscier ◽  
S Johnson
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Karyotype Analysis ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Chromosome Translocations ◽  
Blast Cells ◽  
Inguinal Lymphadenopathy

Abstract A 21-yr-old man presented with inguinal lymphadenopathy and splenomegaly. The peripheral blood showed a high blast cell count. The morphological and immunologic features of the blast cells were consistent with the diagnosis of common acute lymphoblastic leukemia (ALL) with 15% pre-B-cells. Banded karyotype analysis of the blood and the marrow cells, using the technique of methotrexate synchronization, revealed the presence of (8;14) and (14;18) chromosome translocations, a finding that has not been previously documented. The significance of these findings is discussed.

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.

scholarly journals Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa M. Zahran ◽  
Azza Shibl ◽  
Amal Rayan ◽  
Mohamed Alaa Eldeen Hassan Mohamed ◽  
Amira M. M. Osman ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Suppressor Cells ◽  
Healthy Controls ◽  
Blast Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

Role of Matrix Metalloproteinase MMP-2, MMP-9 and Tissue Inhibitor of Metalloproteinase (TIMP-1) in Clinical Progression of Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
Maha Saleh ◽  
Mohamed Khalil ◽  
Mona S. Abdellateif ◽  
Emad Ebeid ◽  
Eman Z. Kandeel
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Count ◽  
Cancer Progression ◽  
Lymphoblastic Leukemia ◽  
Multivariate Logistic Regression Analysis ◽  
Blast Cell ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Pediatric All

Abstract Background: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed.Methods: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- CSCs were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, P<0.001], and CSCs CD84+CD38- [1 (0.03-18.6) versus 0.3 (0.01-1.1), P<0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, AUC of MMP-2 were (80.3%, 53.3% and 0.568, P=0.404), and that of MMP-9 were (53.9%, 40% and 0.660, P=0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, P<0.001), and that of CSCs CD34+ CD38- were (78.9%, 73.3% and 0.855, P<0.001). There was a significant association between MMP-2 overexpression and MRD at day-15, increased BM blast cell count at diagnosis and at day-15, (P=0.020, P=0.047 and P=0.001). Increased TIMP-1 expression associated with the high-risk disease (P<0.001), increased BM blast cell count at diagnosis and at day-15 (P=0.033 and P=0.001), as well as MRD at day 15 and day 42 (P<0.001 for both). CD34+CD38- CSCs associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (P=0.015, P=0.005 and P=0.003). TIMP-1 overexpression associated with shorter DFS and OS rates (P=0.009 and P=0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, P=0.046], and CD34+CD38- CSCs [OR: 6.873, P=0.005] are independent diagnostic factors for pediatric ALL.Conclusion: TIMP-1 and CD34+CD38- CSCs could be useful independent diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

scholarly journals Acute lymphoblastic leukemia with pre-B-cell characteristics

Blood ◽  
1979 ◽  
Vol 54 (1) ◽  
pp. 269-273 ◽  
Author(s):  
JC Brouet ◽  
JL Preud'homme ◽  
C Penit ◽  
F Valensi ◽  
P Rouget ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cells ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Light Chains ◽  
Surface Immunoglobulins ◽  
Blast Cells ◽  
B Cell Precursors

Abstract Blast cells from 6 of 50 patients with acute lymphoblastic leukemia (ALL) displayed intracytoplasmic mu chains in the absence of detectable light chains and surface immunoglobulins. These cells also expressed lalike and common ALL antigens. Terminal deoxynucleotidyltransferase was detectable in 2 of 5 cases tested. These blast cells are probably related to early B-cell precursors (pre-B cells). In 4 of 6 cases the disease had a tumoral presentation; the prognostic significance of this new subgroup, which accounts for 20% of patients with non-T non-B ALL, remains to be established.

Different Activation of WNT Signaling Pathway in B-Cell and T-Cell Acute Leukemias.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4317-4317
Author(s):  
Muge Sayitoglu ◽  
Ozden Hatirnaz ◽  
Yucel Erbilgin ◽  
Fatmahan Atalar ◽  
Ugur Ozbek
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Wnt Signaling ◽  
B Cell ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Wnt Signaling Pathway ◽  
Hematopoietic Cells ◽  
Expression Levels

Abstract WNT signaling pathway proteins function as hematopoietic growth factors and regulate proliferation in normal T-cell and B-cell development. Recent experimental evidence demonstrated that oncogenic transformation in leukemias of both lymphoid and myeloid lineages is dependent on WNT signaling. Not much is known about activation of WNT signaling pathway, its ligands and receptors in hematopoiesis and leukemia pathogenesis. To define its role in leukemia, we aimed to determine mRNA levels of the critical members of WNT pathway (WNT5A, WNT10B, FZ5, β catenin, APC, TCF-1 and LEF-1) by using quantitative real time PCR in acute lymphoblastic leukemia (ALL) patients (T-cell n=42, B-cell n=46 and pre B-cell n=30) and normal hematopoietic cells (bone marrow n=6, peripheral blood n=10, and CD19+ cells from peripheral blood). These genes expressed varying levels in B-cells, preB-cells and T-cells. In the B-cell leukemia patients, WNT5A was expressed notably (OR=58.05 CI 95% 1.63–1219.55, p&gt;0,001). WNT5A directs Ca++ dependent signaling by PKC and a G protein dependent manner which is an alternative pathway for beta-catenin mediated signaling. Also LEF-1 levels were higher in B-ALL patients and APC expression was down regulated when compared to normal tissue (OR=18.81 CI 95% 0.34–5703, p&gt;0.001 and OR=0.212 CI 95% 0.006–8.816, p=0.001, respectively). It is known that LEF-1 blocks APC mediated β catenin nuclear export and activates transcription of various transforming genes, including cyclin, D1, c-myc, MMP7, and LEF-1 itself. WNT5A or WNT10B proteins were not found to be up regulated in preB-ALL whereas APC and LEF-1 gene expressions were increased compared to normal hematopoietic cells (OR=32.97 CI 95% 0.27–1281, 38 p&gt;0.001 and OR=5.57 CI 95% 0.28–89.51, p=0.01, respectively). We found increased TCF-1 expression (7.4 fold) without any β catenin accumulation in T-ALL patients. It is known that TCF-1 in absence of β catenin functions as a tumor suppressor gene. WNT5A, APC and LEF-1 gene expression levels were also different between T-cell, B-cell and preB cell ALL cases. WNT5A expression had the highest levels in B-ALL compared to T-ALL cases, whereas the highest APC expression levels were observed in preB and T-ALL patients. Also LEF-1 expression levels were significantly different between preB and T-cell ALL patients. Taken together these results indicate that WNT signaling genes have abnormal expression and are active in acute lymphoblastic leukemia. This data suggests different WNT activation mechanisms exist in the leukemic transformation in different hematopoietic cells.

Eight Years Experience in External Quality Assessment Scheme (EQAS) for Peripheral Blood Morphology

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4684-4684
Author(s):  
Gabriela Gutierrez ◽  
Anna Merino ◽  
Alicia Domingo ◽  
Josep M Jou ◽  
Joan C Reverter
Keyword(s):  
B Cell ◽  
Sickle Cell ◽  
Peripheral Blood ◽  
Blood Smear ◽  
Lymphoblastic Leukemia ◽  
Lymphoid Cells ◽  
External Quality Assessment Scheme ◽  
Blood Morphology ◽  
Cell Neoplasm ◽  
Blast Cells

Abstract Introduction: The Asociación Española de Hematología y Hemoterapia (AEHH) organizes a National Haematology EQAS and the Hospital Clinic of the University of Barcelona (HCB) serves as the EQAS Coordination Centre (CC). We report results from the eight year long study and the evaluation of laboratory performance for blood smear interpretation by the Spanish haematology EQAS. Objectives: To evaluate: The overall performance of different laboratories in identifying pathological blood cells and If their performance improves for following samples. Material and methods: During the period 2000–2008, replicates of 30 different stained blood smears were sent to 604 EQAS participants for cell morphology evaluation. The samples included blood films from patients with the following diagnoses: acute myeloid leukemia (AML: 8), acute lymphoblastic leukemia (ALL: 3), myeloproliferative disease (MPD: 7), Sézary disease: 3, B cell neoplasm: 4, Plasmodium falciparum infection: 3, and sickle cell disease: 2. Patient details corresponding to the samples were disclosed, such us sex, age, haemoglobin value and white blood cell count. The participants were asked to select up to four significant morphology features using the coding list provided by the EQAS CC. At the end of the run the participants received a brief clinical history of the patient, the final diagnosis and the reference results. For each survey, individual results were assessed against the morphological reference results established by the Cytology group of the AEHH. We divided the participants into two groups according their services to hospitalized (HPL) or non-hospitalized patients (NHPL) in order to compare the diagnostic accuracy in these different laboratory types. Results: HPL showed higher participation ratios and better performance levels than NHPL. For the blood films corresponding to AML and MPD, the presence of blast cells was reported by a mean of 93 % of HPL and 87 % of the NHPL. Only 74% and 65% of the HPL and NHPL respectively reported blast cells in ALL blood films. Nevertheless, the performance of the participants in the diagnosis of ALL showed an improvement in the successive surveys. In the T-neoplasm smears, a mean of 64 % of HPL and 44 % of NHPL reported either Sézary cells or atypical lymphocytes. In addition, not improvement was noted in successive surveys of Sézary disease. Morphological reports for B cell neoplasm slides showed that atypical lymphocyte cells were detected by 56 % and 34 % of HPL and NHPL respectively. Mean values of correct answers in HPL and NHPL for Plasmodium slides were 90 and 78 % respectively, without improvement of the performance in the successive surveys. In sickle cell anaemia samples, a mean of 72 % and 69 % of HPL and NHPL reported abnormal red cells, showing better performances for following samples. Conclusions: Pathological lymphoid cells were the most difficult to identify and our results confirmed the importance of the immunophenotyping in the diagnosis of lymphoproliferative disorders. Our experience of EQAS for peripheral blood morphology showed higher participation and better performance level in HPL with respect to HPL and this observation probably is in relation with the higher degree of haematology specialization in HPL. Since blood smear observation is a crucial tool in the diagnosis of the haematological disorders, specific educational programs aimed to improve peripheral blood morphology analysis should be considered.

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 A colony assay for blast cell progenitors in non-B non-T (common) acute lymphoblastic leukemia

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 823-829
Author(s):  
CA Izaguirre ◽  
J Curtis ◽  
H Messner ◽  
EA McCulloch
Keyword(s):  
Cell Culture ◽  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Proliferative Capacity ◽  
Self Renewal ◽  
Colony Assay ◽  
Blast Cells

A clonal method in cell culture is described that permits the quantitation of blast precursors in common (non-T, non-B) ALL; the method also yields information about progenitor properties, based on analysis of cells in colonies. The technique is identical to that used successfully for normal and malignant B-cell progenitors except that it requires culture at below O2 tension (5%-7%); mononuclear cells from blood or marrow are depleted of T cells and cultured with media conditioned by T cells in the presence of phytohemagglutinin and irradiated T cells. Cultures are incubated for 5–7 days in a moist atmosphere at 5% CO2 and 5%-7% O2. Colonies were obtained from marrow or blood of 16 of 18 ALL patients. Cells in colonies had the same characteristics (E-, slg-, cALL+ and clgM+ or clgM-) as the cells in the patient. By replating pooled colonies, self-renewal of progenitors was shown. The findings are considered in light of a model of leukemic blasts that depicts such populations as lineages maintained by progenitors that either renew themselves or give rise to blast cells with little or no proliferative capacity.

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