The Aplastic Presentation of Childhood Leukaemia: a Feature of Common‐ALL

Breatnach, F.; Chessells, Judith M.; Greaves, MF

doi:10.1111/j.1365-2141.1981.tb07241.x

Cited by 78 publications

(42 citation statements)

References 13 publications

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“…In addition to this extreme situation when very few CI)lObr'@" cells are sufficient to suggest the diagnosis ofALL, in a further 20-25% of cases median CD 10 AgE has significantly been above the normal range but with some overlap (30). This test is likely to be a valued diagnostic tool in "smoldering" leukemia (31,32 ). An important potential pitfall is, however, that in regenerating BM samples following chemotherapy some precursors and mostly SIg+, TdT-B lymphocytes may express CDlO with particularly high CDlO intensity ( 27.33).…”

Section: Discussionmentioning

confidence: 99%

Leukemia‐associated changes identified by quantitative flow cytometry: I. CD10 expression

et al. 1994

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We have compared CDlO antigen expression in normal fetal bone marrow with that of B-lineage acute lymphoblastic leukemia (ALL). Both quantitative indirect immunofluoresence (QIFI) and direct immunofluorescence (IF) tests with Quantum beads were used to convert median fluorescence intensity (MFI) values into numbers of antigen molecules expressed per cell (AgE). Lymphoid precursors in the fetal marrow and liver expressed 3-12.5 x lo3 CD10 molecules/cell with an upper limit of 5 x 104/cell (MaxAgE). The median CDlO AgE in the different cases of acute B-lineage ALL were variable and ranged from undetectable to very high values (> 1.8 x lo5). In 24 of the 72 cases (33%) tested with QlFl the median CDlO AgE was above the highest values seen in normal samples (> 5 x 104/cell). An additional 23.6% of cases had higher median values than the normal median C D l O AgE. Next, CDlO antigen was quantitated in 78 cases during the routine multiparameter analysis of 8-lineage leukemia using CD1 O/class ll/CD34 3-color IF test or CDlO/TdT 2-color IF test. The aberrant overexpression was confirmed in 43.6% of ALL cases. The CDIObright display suggested ALL diagnosis even when few cells were available for study, e.g., in early relapse and in ALL masquerading as aplastic anemia. The levels of CDlO expression were maintained in relapse. In addition, different C D l O levels were associated with the various chromosomal alterations: high C D l O levels (> 3 x 104/cell) with hyperdiploidy, low CDlO levels ( 1 . 8 4 x 103/cell) with the t(1;191, and undetectable levels (< 1.2 x 103/cell) with the t(4;11) translocations. These findings show that while all these diseases are part of the precursor B-cell spectrum, the CDlO changes are linked to disease-associated alterations instead of truly reflecting the features of subtypes of normal B-cell precursors. The quantitative CDlO assessment should therefore be part of the routine flow cytometric assessment in ALL, and further careful studies are warranted during the regeneration phase following chemotherapy. High CDlO expression alone during strong bone marrow regeneration may not be leukemia specific and both the multiparameter analysis described above and parallel studies for gene rearrangements will be necessary to establish the relative values of these assays in detecting minimal disease amidst regenerating marrow. 0 1994 Wiley-Liss, Inc.Key terms: CD10, acute lymphoblastic leukemia, minimal residual disease, immunodiagnosis, flow cytometry, quantimetrySince the discovery of B precursor cell-associated molecules such as common acute lymphoblastic leukemia (ALL) antigen (referred to as CDlO and neutral endopeptidase) (1,2), CD34 antigen (3-5), and nuclear terminal transferase ( TdT) ( 1,6) it has been emphasized that these differentiation antigens are expressed on normal immature cells and retained on the corresponding malignancies. At the same time, the strikingly high expression of CDlO antigen on occasional cases of ALL has been recorded on the microscope (6) or by flow cytometry (7) bu...

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Section: Discussionmentioning

confidence: 99%

Leukemia‐associated changes identified by quantitative flow cytometry: I. CD10 expression

et al. 1994

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“…Occasional cases of marrow hypoplasia or aplasia in childhood subsequently evolve into a frankly leukaemic phase, usually acute lymphoblastic leukaemia (ALL) (Melhorn et al, 1970;Breatnach et al, 1981;Saarinen & Wegelius, 1981;Klingemann et al, 1986;Cheng et al, 1987;Reid & Summerfield, 1992;D'Alessio et al, 1993;Liang et al, 1993;Matloub et al, 1993;Sato et al, 1993). In some cases the leukaemia becomes evident after a prolonged period of hypoplasia, but in others the patient appears to recover only to subsequently develop leukaemia.…”

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confidence: 99%

Leukaemia presenting as marrow hypoplasia: molecular detection of the leukaemic clone at the time of initial presentation

et al. 1997

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Summary. Occasional cases of transient marrow hypoplasia in childhood evolve into acute leukaemia. We studied two children who presented with marrow hypoplasia following infection and who developed acute lymphoblastic leukaemia 2-3 months later. A simple polymerase-chain-reaction (PCR) test for monoclonality showed that immunoglobulin heavychain gene rearrangements of the same size were present at the times of both hypoplasia and leukaemia, and DNA sequencing confirmed identity of these rearrangements. PCR-based quantification, using patient-specific primers, showed in both patients that the leukaemic clone made up 20-25% of the marrow cells during hypoplasia. In contrast, four patients with typical aplastic anaemia showed only polyclonal B-cell populations in the marrow. We conclude that the leukaemic clone was already present at the time of hypoplasia in the two index patients and that in future a simple PCR test for monoclonality could be used to screen patients with marrow aplasia or hypoplasia for the presence of a monoclonal B-cell population. Patients with monoclonal populations could then be monitored carefully for subsequent development of leukaemia.

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“…This suggests that the use of the combined assessment of these markers by QFC may distinguish more precisely between normal and leukemic B-precursors than the nonquantitative methods of flow cytometry, especially in the analysis of samples from children, who present a high percentage of normal B-precursors in BM that mimic the immunophenotypic features of ALL (11,32). Moreover, the approach described here may be useful in those cases of ALL presenting with pancytopenia, a condition of difficult diagnosis by morphological analysis alone (17,18).…”

Section: Discussionmentioning

confidence: 94%

“…The introduction of quantitative fluorescence cytometry (QFC) techniques allowed quantifying antigen expression in an accurate and reproducible manner (13,14) and previous reports have suggested that leukemic cells may express antigens at densities distinct from those presented by their normal counterparts (4,15,16). This method may be useful for MRD detection, as well as for the diagnosis of ALL, especially in those cases preceded by transient pancytopenia, a presentation more common in children and of difficult diagnosis (17,18).…”

Section: Introductionmentioning

confidence: 99%

Immunophenotype of normal and leukemic bone marrow B-precursors in a Brazilian population. A comparative analysis by quantitative fluorescence cytometry

Rego

Garcia

Carneiro

et al. 2001

Braz J Med Biol Res

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The distinction between normal and leukemic bone marrow (BM) Bprecursors is essential for the diagnosis and treatment monitoring of acute lymphoblastic leukemia (ALL). In order to evaluate the potential use of quantitative fluorescence cytometry (QFC) for this distinction, we studied 21 normal individuals and 40 patients with CD10 + ALL. We characterized the age-related changes of the CD10, CD19, TdT, CD34 and CD79a densities in normal and leukemic BM. Compared to normal adults, the B-precursors from normal children expressed significantly lower values of CD34-specific antibody binding capacity (SABC) (median value of 86.6 vs 160.2 arbitrary units (a.u.) in children and adults, respectively). No significant age-related difference was observed in the expression of the other markers in the normal BM, or in any of the markers in the leukemic BM. Based on the literature, we set the cut-off value for the normal CD10 expression at 45 x 10 3 a.u. for both age groups. For the remaining markers we established the cut-off values based on the minimum-maximum values in the normal BM in each age group. The expression of CD10 was higher than the cut-off in 30 ALL cases and in 18 of them there was a concomitant aberrant expression of other markers. In 9 of the 10 CD10 + ALL with normal CD10 SABC values, the expression of at least one other marker was aberrant. In conclusion, the distinction between normal and leukemic cells by QFC was possible in 38/40 CD10 + ALL cases.

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The Aplastic Presentation of Childhood Leukaemia: a Feature of Common‐ALL

Cited by 78 publications

References 13 publications

Leukemia‐associated changes identified by quantitative flow cytometry: I. CD10 expression

Leukemia‐associated changes identified by quantitative flow cytometry: I. CD10 expression

Leukaemia presenting as marrow hypoplasia: molecular detection of the leukaemic clone at the time of initial presentation

Immunophenotype of normal and leukemic bone marrow B-precursors in a Brazilian population. A comparative analysis by quantitative fluorescence cytometry

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