scholarly journals Prethymic Cytoplasmic CD3 Negative Acute Lymphoblastic Leukemia or Acute Undifferentiated Leukemia: A Case Report

2011 ◽  
Vol 2011 ◽  
pp. 1-4
Author(s):  
Elisa Cannizzo ◽  
Giovanni Carulli ◽  
Luigi Del Vecchio ◽  
Antonio Azzarà ◽  
Sara Galimberti ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Case Report ◽  
Acute Leukemia ◽  
Gene Rearrangement ◽  
Germ Line ◽  
Lymphoblastic Leukemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Line Configuration ◽  
Hla Dr ◽  
Molecular Studies

Acute undiffentiated leukemia (AUL) is an acute leukemia with no more than one membrane marker of any given lineage. Blasts often express HLA-DR, CD34, and/or CD38 and may be positive for terminal deoxynucleotidyl transferase (TdT). The expression of CD34, HLA-DR, and CD38 has been shown in pro-T-ALL, although in this case, blasts should also express CD7 and cyCD3. However, some cases of T-ALL without CD3 in the cytoplasm and all TCR chain genes in germ line configuration are reported, features that fit well with a very early hematopoietic cell. We report a case of acute leukemia CD34+/−HLADR+CD7+CD38+cyCD3− in which a diagnosis of AUL was considered. However the blasts were also positive for CD99 and TCR delta gene rearrangement which was found on molecular studies. Therefore a differential diagnosis between AUL and an early cyCD3 negative T-ALL was debated.

scholarly journals Clinical and laboratory characteristics of acute leukemia with the 4;11 translocation

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 689-697 ◽  
Author(s):  
J Mirro ◽  
G Kitchingman ◽  
D Williams ◽  
GJ Lauzon ◽  
CC Lin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
Immunoglobulin Gene Rearrangement

Abstract This report describes the clinical and laboratory features of seven cases of acute leukemia associated with the 4;11 chromosomal translocation. All seven children had acute lymphoblastic leukemia by standard morphologic and cytochemical criteria. Leukemic blasts from six of seven patients were terminal deoxynucleotidyl transferase- positive. Immunologic phenotyping suggested the leukemias were of B cell origin; blasts from five patients expressed HLA-DR and p24 (CD-9 antibody), blasts from three patients expressed B4 (CD-19), and blasts from two patients expressed the common acute lymphoblastic leukemia antigen (CD-10). One patient's leukemic blasts contained cytoplasmic immunoglobulin. Analysis of DNA from four of five patients demonstrated additional evidence of B cell differentiation with heavy-chain immunoglobulin gene rearrangement. When DNA from the four patients with heavy-chain immunoglobulin gene rearrangement was analyzed, one patient's DNA demonstrated light-chain immunoglobulin gene rearrangement. However, flow cytometric analysis of blasts from three patients showed the simultaneous expression of the lymphoid-associated antigen B4 (CD-19) and the myeloid-associated antigen My-1 (X-Hapten). Electron microscopic examination of blasts from one patient that expressed both lymphoid- and myeloid-associated antigens demonstrated ultrastructural characteristics of both lineages. These findings suggest that acute leukemia with the t(4;11) abnormality has mixed lineage characteristics as a result of leukemogenesis in a multipotential progenitor cell or aberrant gene expression later in differentiation. Furthermore, serial analysis of karyotype, immunophenotype, and heavy-chain immunoglobulin genes revealed changes in these biologic markers over time, suggesting continued chromosome rearrangement and gene modulation after the leukemogenic event in cells with the t(4;11).

scholarly journals Clinical and laboratory characteristics of acute leukemia with the 4;11 translocation

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 689-697
Author(s):  
J Mirro ◽  
G Kitchingman ◽  
D Williams ◽  
GJ Lauzon ◽  
CC Lin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
Immunoglobulin Gene Rearrangement

This report describes the clinical and laboratory features of seven cases of acute leukemia associated with the 4;11 chromosomal translocation. All seven children had acute lymphoblastic leukemia by standard morphologic and cytochemical criteria. Leukemic blasts from six of seven patients were terminal deoxynucleotidyl transferase- positive. Immunologic phenotyping suggested the leukemias were of B cell origin; blasts from five patients expressed HLA-DR and p24 (CD-9 antibody), blasts from three patients expressed B4 (CD-19), and blasts from two patients expressed the common acute lymphoblastic leukemia antigen (CD-10). One patient's leukemic blasts contained cytoplasmic immunoglobulin. Analysis of DNA from four of five patients demonstrated additional evidence of B cell differentiation with heavy-chain immunoglobulin gene rearrangement. When DNA from the four patients with heavy-chain immunoglobulin gene rearrangement was analyzed, one patient's DNA demonstrated light-chain immunoglobulin gene rearrangement. However, flow cytometric analysis of blasts from three patients showed the simultaneous expression of the lymphoid-associated antigen B4 (CD-19) and the myeloid-associated antigen My-1 (X-Hapten). Electron microscopic examination of blasts from one patient that expressed both lymphoid- and myeloid-associated antigens demonstrated ultrastructural characteristics of both lineages. These findings suggest that acute leukemia with the t(4;11) abnormality has mixed lineage characteristics as a result of leukemogenesis in a multipotential progenitor cell or aberrant gene expression later in differentiation. Furthermore, serial analysis of karyotype, immunophenotype, and heavy-chain immunoglobulin genes revealed changes in these biologic markers over time, suggesting continued chromosome rearrangement and gene modulation after the leukemogenic event in cells with the t(4;11).

scholarly journals Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 21-31 ◽  
Author(s):  
RC Stong ◽  
SJ Korsmeyer ◽  
JL Parkin ◽  
DC Arthur ◽  
JH Kersey
Keyword(s):  
Acute Leukemia ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
A Cell ◽  
B Lineage

Abstract A cell line, designated RS4;11, was established from the bone marrow of a patient in relapse with an acute leukemia that was characterized by the t(4;11) chromosomal abnormality. The cell line and the patient's fresh leukemic cells both had the t(4;11)(q21;q23) and an isochromosome for the long arm of No. 7. Morphologically, all cells were lymphoid in appearance. Ultrastructurally and cytochemically, approximately 30% of the cells possessed myeloid features. The cells were strongly positive for terminal deoxynucleotidyl transferase. They were HLA-DR positive and expressed surface antigens characteristic for B lineage cells, including those detected by anti-B4, BA-1, BA-2, and PI153/3. Immunoglobulin gene analysis revealed rearrangements of the heavy chain and kappa chain genes. The cells lacked the common acute lymphoblastic leukemia antigen and antigenic markers characteristic of T lineage cells. The cells reacted with the myeloid antibody 1G10 but not with other myeloid monoclonal antibodies. Treatment with 12-O-tetradecanoyl- phorbol-13-acetate induced a monocyte-like phenotype demonstrated by cytochemical, functional, immunologic, and electron microscopic studies. The expression of markers of both early lymphoid and early myeloid cells represents an unusual phenotype and suggests that RS4;11 represents a cell with dual lineage capabilities. To our knowledge, RS4;11 is the first cell line established from t(4;11)-associated acute leukemia.

scholarly journals Induction of HLA-DC/DS (LEU 10) antigen expression by human precursor B cell lines.

1983 ◽  
Vol 158 (5) ◽  
pp. 1757-1762 ◽  
Author(s):  
C Y Wang ◽  
A Al-Katib ◽  
C L Lane ◽  
B Koziner ◽  
S M Fu
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Antigen Expression ◽  
Fold Increase ◽  
Cell Interaction ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Hla Dr

The expression of HLA-DC/DS antigen detected by the monoclonal antibody Leu 10 was studied in three human precursor and pre-B cell lines (Josh 7, Reh, and Nalm 12). Flow cytometric analysis showed that none of these cell lines stained for the HLA-DC/DS antigen. In the presence of 1.6 X 10(-9) M of 12-O-tetradecanoylporbol-13-acetate (TPA), expression of this antigen was detected. The expression was completed after 168 h of incubation. Iodination of cell surface, immunoprecipitation by Leu 10 antibody, and two-dimensional gel analysis revealed that TPA-treated Josh 7 cells synthesized and expressed a 29,34 kD bimolecular complex with both alpha and beta chains different from those of HLA-DR antigen. Quantitative absorption experiments with cell lysates indicated a greater than 25-fold increase in HLA-DC/DS antigen in TPA-treated cells. With the induction of HLA-DC/DS antigen expression, there are concomitant decreases in the expression of the common acute lymphoblastic leukemia antigen (CALLA) and the enzymatic activity of terminal deoxynucleotidyl transferase. No appreciable changes in HLA-DR and Ig expression were observed. There was also no change in HLA-SB expression as detected by antibody ILR-1. However, DNA synthesis was markedly inhibited by TPA treatment. These results indicate that precursor and pre-B cell lines can be induced to mature in vitro. They also suggest that the expression of HLA-DC/DS antigen which precedes the expression of membrane Ig and follows the HLA-DR expression is relevant to human B cell development and cell interaction.

scholarly journals Phenotypic heterogeneity of TDT+ cells in the blood and bone marrow: implications for surveillance of residual leukemia [see comments]

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 312-319
Author(s):  
RG Smith ◽  
RL Kitchens
Keyword(s):  
Bone Marrow ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Normal Blood ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Hla Dr ◽  
Lineage Markers ◽  
Minimal Residual

Terminal deoxynucleotidyl transferase (TdT) is a useful marker for normal lymphocyte precursors and acute lymphoblastic leukemia (ALL). Our previous studies, however, have shown that for monitoring minimal residual disease in the circulation, assay for TdT alone is not sufficiently specific to distinguish leukemia cells from the background of rare normal blood TdT+ cells. In an attempt to increase specificity for leukemic cells, we have used double and triple immunophenotypic analysis to characterize normal circulating and bone marrow TdT+ cells. Overall, normal TdT+ cells were about 1000-fold more frequent in the marrow than in the blood. More than 75% of TdT+ cells in both the blood and marrow expressed the CD34, CD22, and HLA-DR antigens. However, circulating TdT+ cells infrequently expressed CD19 (4.5%) and CD9 (2.3%), compared with their marrow counterparts (74% and 47%, respectively). The brightly staining CD10+ phenotype, frequently associated with ALL blasts, was significantly less common among normal blood (5.7%) than marrow (31%) TdT+ cells. Although T-lineage markers were rarely expressed on TdT+ cells in either site, CD7+ cells were far more prevalent within the circulating TdT+ subset (4%) than among the marrow population (less than 0.2%). The results suggest a selective release of lineage-uncommitted and/or thymus-destined TdT+ cells from the marrow into the circulation. Moreover, since CD19, CD9, and high- density CD10 are frequently found on ALL blasts, staining for these markers on TdT+ cells in the circulation should improve the specificity of assay for residual common ALL cells. Likewise, assay for CD5+ and possibly CD7+ TdT+ cells in either marrow or blood should provide a very sensitive method of detection of T-ALL blasts.

Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia [see comments]

Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1247-1258
Author(s):  
E Thiel ◽  
BR Kranz ◽  
A Raghavachar ◽  
CR Bartram ◽  
H Loffler ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Sheep Erythrocyte ◽  
Treatment Protocol ◽  
Cell Lineage ◽  
T Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Hematopoietic Progenitor Cell ◽  
Hla Dr

Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia (ALL) were immunophenotyped as part of a prospective treatment protocol study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation, but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins mostly in perinuclear accumulation. The T- cell surface antigens CD5 and/or CD2 and focal acid phosphatase were additional markers of this subgroup traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell markers, namely terminal deoxynucleotidyl transferase (TdT), and in part common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique antigen of marrow cells absent in thymus cells, further characterized this immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was supported by germ-line T-cell receptor beta genes found in 21 of 36 patients analyzed. In five cases only T gamma-chain genes were rearranged. Fifteen patients, however, had rearrangements of both T beta and T gamma genes. Immunoglobulin heavy chain genes were rearranged only in two cases. Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting clinical features, namely mediastinal mass, lymphoadenopathy, and platelet count, and independently of clinical factors in prognosis (P = .02, median remission duration: 15.7 v 33.5 months, and P = .02, median survival time: 24.6 v 50.7 months). We conclude that ALL classification based solely on T- or B-cell lineage affiliation is not sufficient but needs further subdivision according to relevant maturation stages as exemplified here within the T-cell axis. The putative prethymic T cell progenitor phenotype described might help elucidate the sequence of genetic events that commit normal hematopoietic cells to the T-cell lineage.

scholarly journals Shifts in blast cell phenotype and karyotype at relapse of childhood lymphoblastic leukemia [published erratum appears in Blood 1987 Mar;69(3):996]

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1306-1310 ◽  
Author(s):  
CH Pui ◽  
SC Raimondi ◽  
FG Behm ◽  
J Ochs ◽  
WL Furman ◽  
...  
Keyword(s):  
Clonal Selection ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Cell Phenotype ◽  
Frequent Change ◽  
Lineage Switch ◽  
Hla Dr ◽  
Blast Cells ◽  
Acute Nonlymphoblastic Leukemia

Abstract Analyses of bone marrow blast cells collected at diagnosis and relapse from 68 children with acute lymphoblastic leukemia (ALL) demonstrated changes in the expression of cell markers in one-fourth of the patients. Loss of the common ALL antigen (CALLA) was a frequent change, occurring in 8 of the 51 cases initially classified as common or pre-B ALL. The HLA-DR antigen was either acquired or lost in 5 of the 68 cases, terminal deoxynucleotidyl transferase was lost in 6 of 25 cases, and reactivity of the T10 antigen with monoclonal antibodies was increased in 6 of 17 cases of non-T cell ALL. Conversion to acute nonlymphoblastic leukemia, so-called lineage switch, was noted in two cases of common ALL and one of pre-B ALL, coinciding with the loss of CALLA. Results of chromosomal analyses in cases with a loss of CALLA implicated several mechanisms in the observed phenotypic changes. In six cases, including each instance of lineage switch, the original karyotype had been replaced by an entirely different abnormal karyotype, suggesting clonal selection or induction of a second malignancy. In another case, the evidence suggested clonal evolution. Our findings demonstrate that sequential phenotypic and cytogenetic studies may yield valuable insights into the mechanisms of leukemic recurrence and may have implications for treatment selection.

scholarly journals ImmunoglobulinλGene Rearrangement Can PrecedeκGene Rearrangement

1990 ◽  
Vol 1 (1) ◽  
pp. 53-57 ◽  
Author(s):  
Jörg Berg ◽  
Mindy Mcdowell ◽  
Hans-Martin Jäck ◽  
Matthias Wabl
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Light Chain ◽  
Gene Rearrangement ◽  
Germ Line ◽  
Stochastic Theory ◽  
Chain Gene ◽  
Light Chain Gene ◽  
Line Configuration ◽  
Chain Gene Rearrangement

Immunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci:κandλ.It has been reported thatκloci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearrangedλ-chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at theκlocus, and that only upon failure to produce a functionalκchain is there an attempt to rearrange theλlocus; and (b) the stochastic theory, which postulates that rearrangement at theλlocus proceeds at a rate that is intrinsically much slower than that at theκlocus. We show here thatλ-chain genes are generated whether or not theκlocus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.

scholarly journals Occurrence of the common acute lymphoblastic leukemia antigen on blast cells of a patient with chronic myelomonocytic leukemia in non-lymphoid blastic phase

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1482-1484
Author(s):  
V Gressler ◽  
M Garbrecht ◽  
DK Hossfeld
Keyword(s):  
Lymphoblastic Leukemia ◽  
Chronic Myelomonocytic Leukemia ◽  
Leukemic Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunogold Staining ◽  
Hla Dr ◽  
Blastic Phase ◽  
Blast Cells ◽  
Differentiation Pattern ◽  
Myelomonocytic Leukemia

Leukemias showing a conspicuous lymphoid phenotype, ie, those that are HLA-DR positive, common acute lymphoblastic antigen (cALLA) positive, terminal deoxynucleotidyl transferase (TdT) negative, as well as myeloperoxidase positive (MPO), could be considered so-called mixed leukemias. Leukemias with biphenotypic blasts have to be distinguished from cases comprising two separate subpopulations that express different lineage-associated characteristics. By use of a simple new method (Immunogold Staining) we examined a case of chronic myelomonocytic leukemia in blastic phase and demonstrated simultaneous staining for MPO/alpha-naphthyl-esterase and expression of the HLA-DR- positive, cALLA-positive, and TdT-negative phenotype. The cALL antigen was detected only on mono- and myelo-monoblasts; its expression was inversely related to the MPO positivity, and it disappeared together with these types of blasts after chemotherapy. On the basis of our findings it remains obscure whether the cALL antigen at the initial presentation was due to the immature monocytic features of the leukemic cells or disclosed on additional lymphoid differentiation pattern of the blasts.

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