Mixed-Lineage Leukemia and Asynchronous Antigen Expression

Hurwitz, Craig A.; Mirro, Joseph

doi:10.1016/s0889-8588(18)30467-2

Cited by 28 publications

(18 citation statements)

References 147 publications

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“…An exception is observed in abnormal cells that exhibit true lineage infidelity. 37 Usually, the aberrant lineage expression is dimmer than what is found on normal cells, similar to cases of acute myelogenous leukemia (AML) that express CD7 or CD19 with less intensity of expression than the same antigens expressed on lymphoid cells. 2,27 The expression of nonlineage antigens must be interpreted cautiously because some markers are "lineage associated" rather than lineage specific.…”

Section: Descriptions Of Mds Characteristics Used For Flow Cytometry mentioning

confidence: 99%

Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation

Wells

Benesch

Loken

et al. 2003

Blood

327

391

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Marrow cells of myeloid lineage from 115 patients with myelodysplastic syndrome (MDS) were characterized by multidimensional flow cytometry and compared with findings in 104 patients with various disorders and 25 healthy donors. Based on phenotypic and scatter characteristics, a flow cytometric scoring system (FCSS) was developed that allowed for a simple numerical display of results. The flow cytometric scores were categorized as normal/mild (0-1), moderate (2-3), or severe (> 4). Most flow cytometric abnormalities were significantly (P < .05) more frequent in patients with MDS than in the control cohort. Flow cytometric scores in MDS patients were then retrospectively compared with marrow blast counts assessed by morphology, cytogenetics, hematologic parameters, and International Prognostic Scoring System (IPSS) risk categorization. The flow cytometric scores correlated inversely with leukocyte and absolute neutrophil counts (P < .01) and correlated directly with IPSS scores (P < .01) and with IPSS cytogenetic risk categories (P < .01). In 111 MDS patients who underwent allogeneic hematopoietic stem cell transplantation, flow scores correlated with posttransplantation outcome. The probabilities of posttransplantation relapse were 3%, 15%, and 33% for patients with mild, moderate, and severe FCSS scores, respectively (P < .01), and overall survival was 74%, 40%, and 36%, respectively, for the 3 groups (P < .01). In multivariate analyses, there was a significant contribution of the flow score independent of the IPSS in predicting survival and relapse (P < .01, P ‫؍‬ .02, and P ‫؍‬ .03, respectively). These data suggest that FCSS is useful in assessing marrows for diagnosis of MDS and in determining the prognostic outcome in patients with this disorder. (Blood. 2003;102:394-403)

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Section: Descriptions Of Mds Characteristics Used For Flow Cytometry mentioning

confidence: 99%

Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation

Wells

Benesch

Loken

et al. 2003

Blood

327

391

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“…13,14 This has been a particular problem as it has been recognised that the so-called myeloid antigens CD13 and 33 may be present on ALL blasts. [15][16][17] The literature suggests that the incidence of CD13 and/or CD33 positivity is in the order of 5-10% in children and in up to 20% of adult cases. 18 In the UKALLXI trial the overall incidence of such positivity among cases tested was 17%, with only 13% of T cell cases being positive and the highest incidence at 29% occurring in the early pre-B or null cell cases.…”

Section: Figurementioning

confidence: 99%

Analysis of the immunophenotype of children treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia Trial XI (MRC UKALLXI)

Hann

Richards²,

Eden

et al. 1998

Leukemia

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Despite many years of meticulous immunophenotyping of childhood acute lymphoblastic leukaemia (ALL) cases the prognostic significance of some subtypes remains unclear. The Medical Research Council UKALLXI trial (1990)(1991)(1992)(1993)(1994)(1995)(1996) in which uniform treatment has been given to 2090 children with ALL below the age of 18 years and above the age of 1 year, has afforded the opportunity to review these issues. Children with ALL of mature B cell type were not entered into this trial. Immunophenotype analysis was performed in each individual trial centre, but results were centrally reviewed in all cases, and were both available and considered adequate in 1934 (93%) of the first 2090 patients entered. The main diagnostic categories were early pre-B or null reported in 60 cases (3.1%), common ALL in 1242 (64.2%), pre-B in 252 (13.0%), 'common' or pre-B in 172 (8.9%) and T cell in 207 (10.7%) cases. Children with T cell disease were significantly more likely to be over the age of 10 years, with central nervous system disease at diagnosis and to be CD34 negative. They also had a higher incidence of high white cell count and were more likely to be of the FrenchAmerican-British (FAB) L2 morphological subtype. Patients with 'null' cell disease tended to be less than 2 years or greater than 10 years of age, and CD13 and CD33 positive. CD10 was associated with lower white cell count (WBC) at diagnosis, younger age and FAB L1 morphological subtype. The presence of cytoplasmic immunoglobulin in pre-B cells was not associated with any specific clinical or laboratory features. CD34 positivity was less common in T cell patients and was associated with low WBC. Disease-free survival (DFS) and 95% confidence intervals (CI) at 5 years from diagnosis was 52% (95% CI: 44-59%) for T cell disease, 58% (95% CI: 43-73%) for early pre-B (or null cell) disease and 65% (95% CI: 62-68%) for common or pre-B disease; there being no significant difference between common and pre-B disease with regard to disease outcome. Patients with T cell disease had a worse prognosis than any other immunophenotype group (P Ͻ 0.00005). However this worse outcome was no longer significant after allowing for the other principal prognostic factors of age, gender and white cell count at diagnosis except for the very small number with WBC Ͻ20 × 10 9 /l and T cell disease. Those with CD10-positive leukaemia did better than those who were CD10 negative (P Ͻ 0.00005), with DFS at 5 years 64% (95% CI: 62-67%) for positive vs 56% (95% CI: 49-62%) for CD10 negative. CD10 positivity did not have independent significance when white count, gender and age were taken into account. CD13, CD33, and cytoplasmic positivity carried no prognostic significance. Keywords: immunophenotype; prognosis; acute lymphoblastic leukaemia (ALL); children IntroductionImmunological heterogeneity of ALL has been recognised for many years. ing which time the use of standardised panels of antibodies has permitted allocation of more than 98% of leukaemias to their respective lineage...

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“…2,3 The most recently proposed system uses weighted scores assigned to cytochemistry results, surface or cytoplasmic antigen expression, and gene rearrangement analysis. …”

Section: Jbi/iimentioning

confidence: 99%

“…Some have proposed weighted scoring systems for establishing the diagnosis. 2 ' 3 The lack of uniform diagnostic criteria for AMLL and inconsistent diagnostic terminology have contributed to an ongoing controversy regarding the clinical and biologic significance of lymphoid-associated antigen expression in acute myeloid leukemias.…”

mentioning

confidence: 99%

Lymphoid-Associated Antigen Expression by Acute Myeloid Leukemia

Launder¹,

Bray²,

Stempora³

et al. 1996

Am J Clin Pathol

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The expression of lymphoid-associated antigens (LAA) on blasts in acute myeloid leukemia (AML) and myeloproliferative disorders in myeloid blast crisis (MPD/MBC) has often been used to establish a diagnosis of acute mixed lineage leukemia (AMLL). The purpose of this study was to determine the incidence of LAA expression in AML and MPD/MBC (Ly+AML); to assess lymphoid differentiation at the genomic level in Ly+AML; and to compare features of Ly+AML with AML and MPD/MBC lacking these antigens (Ly-AML). Seventy-four consecutive cases of AML and MPD/MBC were reviewed for blast morphology, TdT reactivity, and cytochemistry results. Blast immunophenotyping was performed by multiparameter flow cytometry. Acute myeloid leukemia was subtyped according to the FAB classification. Acute myeloid leukemia and MPD/MBC cases expressing one or more of the following antigens, CD2, CD3, CD5, CD7, CD19, or CD20, were considered to be Ly+AML. Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement studies were performed by Southern blot With the advent of immunophenotyping by flow cytometry in the 1980s, it became evident that many acute myeloid leukemias (AML) express surface antigens usually associated with lymphoid lineage. This discovery led to a series ofreports describing AML with lymphoid antigens (Ly+AML), which have been recently reviewed.' In the majority of the original reports, the aberrant expression of one or more unexpected lymphoid antigens was the primary criterion for inclusion of cases in the reported series. Leukemias expressing so-called aberrant antigens have been variously termed acute biphenotypic leukemia, hybrid leukemia, acute mixed leukemia, acute leukemia of mixed phenotype, or acute mixed lineage leukemia (AMLL).Diagnosis of AMLL based on surface antigen expression was almost immediately confounded by the realization that most surface antigens are lineage associated, Address reprint requests to Dr. Farhi: Department of Pathology, Emory University Hospital, Clifton Road NE, Atlanta, GA 30322. analysis using probes for JH, Jkappa, and JBI/BII. Sixteen of the 74 cases (22%) were identified as Ly+AML. Of these, the T-cell-associated markers CD7, CD2, and CD5 were expressed on 7 (44%), 6 (38%), and 4 (25%) Ly+AML cases, respectively. The B-eell associated markers CD19 and CD20 were expressed on two cases (13%) and one (6%) case, respectively. The FAB subtypes were similarly represented among Ly+AML and Ly-AML. Expression of LAA did not correlate with TdT positivity. In nine cases of Ly+AML (7 expressing T-cellassociated antigens and two expressing B-cell-associated antigens), Southern blot analysis revealed no Ig or TCR gene rearrangements. These results suggest that expression of CD2, CD5, and CD7 in otherwise straightforward AML should not be taken as evidence of lymphoid lineage commitment and does not warrant a diagnosis of AMLL.

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Mixed-Lineage Leukemia and Asynchronous Antigen Expression

Cited by 28 publications

References 147 publications

Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation

Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation

Analysis of the immunophenotype of children treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia Trial XI (MRC UKALLXI)

Lymphoid-Associated Antigen Expression by Acute Myeloid Leukemia

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