Aberrant Immunophenotypes Detected by Flow Cytometry in Acute Lymphoblastic Leukemia

Vela, J. A. Garcia; Monteserin, M. C.; Delgado, I. Pelayo; Benito, Lauren; Oña, F.

doi:10.3109/10428190009148848

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…Using three or four colorcombinations, an aberrant,l eukemia-associated immunophenotype (LAIP)can be identifiedin90-95% of ALL samples (15,25). Garcia Ve la et alfound the coexistenceofatleasttwo aberrancies in leukemic lymphoblasts usingalarge panel of monoclonal antibodies (26). To our knowledge,the detection of across-lineage intracytoplasmic antigeninBCP ALL has not yetbeen published.…”

Section: Discussionmentioning

confidence: 99%

Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit A

Kiss¹,

Hevessy²,

Veszprémi³

et al. 2006

Thromb Haemost

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SummaryBlood coagulation factor XIII (FXIII) is a protransglutaminase circulating asa tetramer formed by two types of subunits (A2B2). The intracellular dimeric form of FXIII (A2) is present in platelets, megakaryocytes, monocytes and macrophages and has been detected in mono-and megakaryocytic leukemias. The aim of our study was to investigate FXIII-A expression in newly diagnosed B cell acute lymphoblastic leukemia (ALL) samples. We examined 47 de novo ALL cases of B cell origin by triple color labeling with flow cytometry. FXIII-A was detected by a FITC conjugated monoclonal antibody combined with CD34 and CD45 staining. In selected cases FXIII-A was investigated on slides prepared from blasts and visualized with a fluorescent microscope. In addition, blasts were studied by Western blot analysis and FXIII-A was measured by a highly sensitive ELISA method. By flow cytometry 19 samples of the 47 cases were found to be FXIII-A positive. Antigen concentration was 3.11± 1.19 fg/blast, while normal lymphoid precursors and mature lymphocytes from B-CLL did not contain FXIII-A. In the lysate of lymphoblasts that were positive by flow cytometry, a single band (82 kDa) corresponding to FXIII-A was detected on Western blots. Confocal laser scanning microscopic examination revealed the presence of FXIII-A in the cytoplasm of these lymphoblasts. This novel expression site of FXIII-A in leukemic lymphoblasts can be utilized as a diagnostic tool and may also gain functional significance in B-lineage ALL.

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Section: Discussionmentioning

confidence: 99%

Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit A

Kiss¹,

Hevessy²,

Veszprémi³

et al. 2006

Thromb Haemost

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“…At present, these are the most sensitive techniques for MRD detection (one leukaemic cell/10 5 −10 6 normal cells), although molecular abnormalities are detectable only in a proportion of ALL patients (Biondi et al , 1992; Campana & Pui, 1995; Gibson et al , 1996; Heid et al , 1996; van Dongen et al , 1999; Foroni et al , 1999; Freeman et al , 1999; Hosler et al , 1999; Martuza et al, 2002). MRD detection by flow cytometry is based on the identification of leukaemia‐associated marker combinations, which are either not expressed or expressed at different levels of intensity by normal BM cells (Syrjälä et al , 1994; Campana & Pui, 1995; Jennings & Foon, 1997; Ciudad et al , 1998a; Campana & Coustan‐Smith, 1999; Griesinger et al , 1999; San Miguel et al , 1999; Garcia Vela et al, 2000; Porwit‐McDonald et al, 2000). A number of studies, using either flow cytometric or molecular approaches, showed that the presence of detectable MRD at any time point during the treatment course can predict relapse in childhood ALL (Biondi et al , 1992; Campana & Pui, 1995; Bear, 1998; Campana & Coustan‐Smith, 1999; van Dongen et al , 1999; Foroni et al , 1999; Griesinger et al , 1999; San Miguel et al , 1999; Coustan‐Smith et al, 2000; Pui & Campana, 2000; Radich, 2000; Sievers & Radich, 2000; Dworzak et al, 2002) and consequently current multicentre protocols have been designed on the basis of MRD monitoring.…”

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confidence: 99%

Outcome prediction by immunophenotypic minimal residual disease detection in adult T‐cell acute lymphoblastic leukaemia

et al. 2002

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Summary. Flow-cytometric detection of minimal residual disease (MRD) identifies patients with high relapse risk in childhood acute lymphoblastic leukaemia (ALL). We studied the efficacy of this method in adult T-ALL treated with the Italian co-operative GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) LAL0496 protocol. Bone marrow samples from 53 patients were taken at fixed treatment time points and MRD was analysed using a leukaemiaspecific immunophenotype (cytoplasmic-CD3/nuclear-terminal desoxynucleotidyl transferase). The median follow-up was 17 months (range 3-61) and a median of 4AE5 analyses/ patient was performed (range 3-12). Six out of 53 (11AE3%) patients were refractory to treatment, 30/53 (56AE6%) relapsed and 17/53 (32AE1%) remain in continuous complete remission. The probability of relapse at 2 years for MRDpositive patients at preconsolidation was 81AE5% vs 38AE9% for MRD-negative patients (P ¼ 0AE00078). This risk was still 54AE5% for MRD-positive vs 15AE8% for MRD-negative patients pre-third reinduction (P ¼ 0AE0098) and 50AE0% for MRDpositive vs 16AE4% for MRD-negative patients pre-sixth reinduction (P ¼ 0AE032). The relapse-predicting value of MRD did not depend on features at diagnosis such as age, sex and leucocyte count. Our data suggest that immunophenotypic MRD monitoring in the first year of treatment is a useful outcome predictor for adult T-ALL patients.

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“…Leukemic cells display phenotypes that are either present in normal precursors or is unique for the leukemic population also referred to as leukemia‐associated immunophenotype (LAIP) or aberrant phenotype. Several publications described LAIP on blasts in acute leukemias (2–5). The major features are lineage infidelity and lineage promiscuity, where leukemic cells express antigens associated with a different cell line, e.g., CD13 and CD33 myeloid‐associated antigens in precursor‐B acute lymphoblastic leukemia (ALL) (6) or CD7 T‐cell marker expression in neoplastic myeloblasts (7).…”

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confidence: 99%

A coagulation factor becomes useful in the study of acute leukemias: Studies with blood coagulation factor XIII

et al. 2007

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The intracellular form of the coagulation factor XIII has previously been identified by immunomorphological techniques using polyclonal antibodies. In these studies, only the A subunit (FXIII-A) was detectable in megakaryocytes/platelets and in monocytes/ macrophages. We developed several novel monoclonal antibody clones directed to both subunits (FXIII-A and FXIII-B) and investigated their appearance in normal and leukemic cells. By using 3-and 4-color flow cytometry FXIII expression was investigated in normal peripheral blood and bone marrow samples and in acute myeloblastic (AML) and lymphoblastic (ALL) leukemia cases. Samples were studied by Western blotting and confocal laser scanning microscopy. With a previously published ELISA assay applying two monoclonal antibodies directed to different epitopes in FXIII-A, we were able to measure the intracytoplasmic content of FXIII-A in normal cells and leukemic blasts. FXIII-A was detectable in normal peripheral blood monocytes and in large quantities in platelets, but both cell types were negative for FXIII-B. There was no surface staining for FXIII-A, it only appeared intracellularly. In samples derived from patients with AML M4 and M5, FXIII-A sensitively identified blast cells. Although normal lymphocytes do not express FXIII-A, 40% of ALL cases showed significant FXIII-A expression as determined by flow cytometry. FXIII-A positivity of lymphoblasts was verified by Western blotting, ELISA, and confocal laser scanning microscopy cytometry. These data provide evidence that FXIII-A is a sufficiently sensitive marker in differentiating myeloblasts and monoblasts and is suitable for identifying leukemia-associated phenotypes in ALL. ' International Society for Analytical CytologyKey terms factor XIII; flow cytometry; acute leukemia phenotype HEMATOLOGICAL malignancies are exceptional in the sense that unlike solid tumors, right from the beginning they are spread all over the body since cancer cells appear in the blood. Acute leukemias represent 85% of all leukemias in children and 45% in adults. In childhood, $80% of acute leukemias are lymphoblastic and 15-20% are myeloblastic (1), whereas this proportion is basically reversed in adults. Leukemic cells display phenotypes that are either present in normal precursors or is unique for the leukemic population also referred to as leukemia-associated immunophenotype (LAIP) or aberrant phenotype. Several publications described LAIP on blasts in acute leukemias (2-5). The major features are lineage infidelity and lineage promiscuity, where leukemic cells express antigens associated with a different cell line, e.g., CD13 and CD33 myeloid-associated antigens in precursor-B acute lymphoblastic leukemia (ALL) (6) or CD7 T-cell marker expression in neoplastic myeloblasts (7). In case of asynchronous differentiation, markers of different maturational stages are expressed simultaneously, like the coexpression of CD10 and CD20 in B-ALL (8) or CD117/CD15 coexpression in acute myeloid leukemia (AML) (9). Antigen

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Aberrant Immunophenotypes Detected by Flow Cytometry in Acute Lymphoblastic Leukemia

Cited by 6 publications

References 26 publications

Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit A

Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit A

Outcome prediction by immunophenotypic minimal residual disease detection in adult T‐cell acute lymphoblastic leukaemia

A coagulation factor becomes useful in the study of acute leukemias: Studies with blood coagulation factor XIII

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