Sensitivity of combined DNA/immunophenotype flow cytometry for the detection of low levels of aneuploid lymphoblastic leukemia cells in bone marrow

Nowak, Ralf; Oelschlaegel, Uta; Schuler, Ulrich S.; Zengler, H.; Hofmann, R.; Ehninger, Gerhard; Andreeff, Michael

doi:10.1002/(sici)1097-0320(19970215)30:1<47::aid-cyto7>3.0.co;2-c

Cited by 20 publications

(12 citation statements)

References 24 publications

(18 reference statements)

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“…For example, the CV of the G0/G1 peak of the CD3-positive cells is significantly lower than the CV of all cells in the bone marrow samples. 19 This is also the case in the PBSC samples, but to a lesser degree (P = 0.036).…”

Section: Discussionmentioning

confidence: 73%

Flow cytometric DNA quantification in immunophenotyped cells as a sensitive method for determination of aneuploid multiple myeloma cells in peripheral blood stem cell harvests and bone marrow after therapy

Nowak

Oelschlägel

Range

et al. 1999

Bone Marrow Transplant

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Summary:The simultaneous measurement of DNA content and myeloma-related antigens (B-B4 or CD38) by flow cytometry is proposed as a method for the detection of aneuploid plasma cells in peripheral blood stem cell (PBSC) harvests and in bone marrow after therapy. In 30 patients with initially detected aneuploid myeloma cells we evaluated the bone marrow after therapy and in eight of these patients 23 PBSC harvests were analyzed. In 13 of 23 PBSC harvests aneuploid myeloma cells were detectable (range: 0.02-0.63%). In the bone marrow of the 30 patients aneuploid plasma cells were detectable in all samples after chemotherapy (range: 0.12-35.70%) and after autologous PBSC transplantation in two of three patients (0.21% and 0.03%). Furthermore the relationship between diploid and aneuploid plasma cells can be evaluated. In the PBSC harvests the percentage of aneuploid plasma cells is significantly lower than that of diploid plasma cells (P = 0.006). In contrast, in bone marrow the aneuploid plasma cells are predominant in most patients even after therapy (24 of 30 patients; P = 0.0055). In the case of initially detected aneuploid myeloma cells, a contamination with malignant cells can be estimated with a simple flow cytometric method in PBSC harvests and in bone marrow after therapy.

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Section: Discussionmentioning

confidence: 73%

Flow cytometric DNA quantification in immunophenotyped cells as a sensitive method for determination of aneuploid multiple myeloma cells in peripheral blood stem cell harvests and bone marrow after therapy

Nowak

Oelschlägel

Range

et al. 1999

Bone Marrow Transplant

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“…In a case report of two patients with aneuploid ALL [41], abnormal DNA content was detectable after induction in the patient who relapsed, while the patient with euploid DNA remained in complete remission. The same authors conducted dilution assays with aneuploid ALL cells from patients [42] in order to test the sensitivity of ploidy analysis. Similar to our findings, ploidy analysis was unsuccessful at dilutions of 51%.…”

Section: Discussionmentioning

confidence: 99%

DNA ploidy analysis as an adjunct for the detection of relapse in B-lineage acute lymphoblastic leukemia

Kenney

Zieske

Rinder

et al. 2008

Leukemia & Lymphoma

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Detection of relapse in acute lymphoblastic leukemia (ALL) is essential for proper management. However, immunophenotypic detection of relapse by flow cytometry in B-lineage ALL can be confounded by several factors, including lack of a unique immunophenotype and modulation of aberrant phenotypes after treatment. We hypothesized that flow cytometric DNA ploidy analysis may detect relapse in aneuploid ALL cases that might be missed by flow immunophenotyping. We retrospectively studied ALL cases at our institution between 1991 and 2003 (n = 114). Aneuploid populations were present at diagnosis in 32% of all patients. Sixty-five percent of all patients had "normal" leukemic immunophenotypes, defined as being similar to normal precursor B-cells, while 35% had "aberrant" immunophenotypes with myeloid or T antigen co-expression. In ALL cases that were originally aneuploid, follow-up ploidy-analysis detected relapsed disease in all cases which were also detected by flow immunophenotyping, suggesting that ploidy analysis is highly sensitive for detecting ALL relapse. However, in 5 cases in which the diagnosis of relapse could not be reliably made by flow immunophenotyping, ploidy analysis successfully detected aneuploid cells, i.e., relapse, in all five; these included 3 patients with normal and 2 with aberrant original immunophenotypes. These results suggest that it may be beneficial to perform ploidy analysis as an adjunct to flow immunophenotyping in following patients with B-lineage ALL who demonstrate aneuploidy at diagnosis.

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“…Such leukemia-associated phenotypes can be identified by double-, triple-, or quadruple-color staining techniques performed with antibodies conjugated to different fluorochromes. Additional capabilities of flow cytometry, such as cell sorting followed by fluorescence in-situ hybridization (FISH) (32), or simultaneous analysis of phenotype and DNA content (33), may also contribute to MRD studies. Differences in the antigenic expression of leukemic cells and normal progenitor cells may be qualitative, quantitative, or both (Tables 2 and 3).…”

Section: Methodologic Issues In Immunologic Detection Of Minimal Resimentioning

confidence: 99%

Detection of minimal residual disease in acute leukemia by flow cytometry

1999

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Patients with acute leukemia in clinical remission may still have up to 1010 residual malignant cells (the upper limit of detection by standard morphologic techniques). Sensitive techniques to detect minimal residual disease (MRD) may allow better estimates of the leukemia burden and help the selection of appropriate therapeutic strategies. Flow cytometry and polymerase chain reaction have emerged as the most promising methods for detecting submicrospopic levels of leukemia. Flowcytometric detection of MRD is based on the identification of immunophenotypic combinations expressed on leukemic cells but not on normal hematopoietic cells. It affords the detection of one leukemic cell among 10,000 normal bone marrow cells, and can be currently applied to at least two thirds of all patients with acute leukemia. Prospective studies in large series of patients have demonstrated a strong correlation between MRD levels during clinical remission and treatment outcome. Therefore, MRD assays can be reliably used to assess early response to treatment and predict relapse. In this review, we discuss methodologic aspects and clinical results of flowcytometric detection of MRD in patients with acute leukemia. Cytometry (Comm. Clin. Cytometry) 38: 139–152, 1999. © 1999 Wiley‐Liss, Inc.

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Sensitivity of combined DNA/immunophenotype flow cytometry for the detection of low levels of aneuploid lymphoblastic leukemia cells in bone marrow

Cited by 20 publications

References 24 publications

Flow cytometric DNA quantification in immunophenotyped cells as a sensitive method for determination of aneuploid multiple myeloma cells in peripheral blood stem cell harvests and bone marrow after therapy

Flow cytometric DNA quantification in immunophenotyped cells as a sensitive method for determination of aneuploid multiple myeloma cells in peripheral blood stem cell harvests and bone marrow after therapy

DNA ploidy analysis as an adjunct for the detection of relapse in B-lineage acute lymphoblastic leukemia

Detection of minimal residual disease in acute leukemia by flow cytometry

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