Lineage switch in acute leukemia

Stass, Sanford A.; Mirro, Joseph; Melvin, Susan L.; Pui, Ching‐Hon; Murphy, Sharon B.; Williams, Dorothy L.

doi:10.1182/blood.v64.3.701.701

Cited by 204 publications

(45 citation statements)

References 23 publications

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“…Detection of atypical antigen expression by double color immunofluorescence implies that the antigenic features identified at diagnosis remain the same during the course of the disease. Differences in the immunophenotype as well as lineage switching in relapsing leukemias have been described previously (6,7,23,26). Of note, the leukemia-associated antigen combinations were retained at relapse in 11 of 12 cases; the only patient with a change in phenotype and FAB-based criteria as well represented a case of AML after MDS.…”

Section: Discussionsupporting

confidence: 54%

Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Drach

Glassl

et al. 1992

Cytometry

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The aim of this study was to investigate to which extent acute leukemias could be monitored for residual disease by using atypical antigen combinations as leukemia-related markers. Atypical antigenic features were determined by double color flow cytometry and included coexpression of lymphoid and myeloid related antigens, unphysiological coexpression of immature and mature antigens, and lack of an antigen that is normally expressed during maturation. Atypical immunophenotypes were detected in 35 of 68 patients with AML (51.5%) and 15 of 24 patients with ALL (62.5%). When 12 patients with leukemia-associated markers were again analyzed at relapse, the relevant antigen combinations were retained in 11 of them. The sensitivity of this two color flow cytometric assay as determined in dilution experiments was 1 in lo3 to lo4 cells.Follow-up studies of bone marrow samples revealed that, after induction chemotherapy cells with leukemia-associated markers were detectable in several patients at a frequency of 0.5 to 4%, but only patients in whom the cells with atypical antigens never disappeared suffered from relapse. In contrast, patients who became negative for the atypical cells remained in complete remission (median remission duration after the first negative bone marrow assessment by flow cytometry 52 weeks, range 20-102).We conclude that atypical antigen combinations, which are present in a meaningful number of acute leukemias, are a valuable means of monitoring acute leukemia patients during follow-up. This flow cytometric approach can complement other strategies to get a more accurate definition of remission in acute leukemia. o 1992 Wiley-Liss, Inc.

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Section: Discussionsupporting

confidence: 54%

Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Drach

Glassl

et al. 1992

Cytometry

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“…The existence of a pluripotent stem-cell capable of differentiation along the myeloid and lymphoid pathways has been suggested based on evidence from cases of biphenotypic leukemia in which a simultaneous or rapid switch from one to another lineage has occurred (Perentesis et al, 1983;Lanham et al, 1984;Stass et al, 1984). The high expression of 3C5 in 3 out of the 4 TdT+ AML cases (Table 2) in which a proportion of cells displayed simultaneously lymphoid (TdT+) and myeloid (SBB and MPO) markers together with the positivity in M1 AML and common ALL suggests that 3C5 is expressed in an early progenitor cell (presumably TdT+) capable of undergoing either B-lymphoid (TdT + , 3C5 + , J5 +) or limited myeloid differentiation TdT + / -,3C5 + , MPO+).…”

Section: Discussionmentioning

confidence: 99%

Characterization of myeloid leukemias with monoclonal antibodies 3C5 and MY9

Matutes

Rodriguez

Polli

et al. 1985

Hematological Oncology

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The expression of two membrane antigens identified by the monoclonal antibodies (McAb) My9 and 3C5 has been investigated in cells from 80 acute leukemias. My9 was positive in the blasts of 33 out of the 38 (87 per cent) cases of acute myeloid leukemia (AML) tested, regardless of FAB subtype, and in 13 of 18 (72 per cent) cases of chronic granulocytic leukemia (CGL) in myeloid blast crisis. The reactivity of 3C5 was confined to myeloblastic (M1) AML, 85 per cent of cases, and to lymphoblastic leukemia (ALL) of B-lineage, 70 per cent of cases, including CGL in lymphoid transformation. My9 was negative in ALL except for an unusual case. The phenotype My9+, 3C5+ was seen exclusively in M1 (69 per cent) and M2 (14 per cent) AML. Ultrastructural analysis with the immunogold method in combination with the myeloperoxidase (MPO) reaction showed that expression of My9 increased in parallel with MPO activity whereas 3C5 was expressed mainly in myeloblasts with little MPO content. We conclude that the use of these two McAb will contribute to the diagnosis and classification of AML and may throw some light to the pathogenesis of biphenotypic acute leukemias, including TdT + AML.

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“…Treatment recommendations for lineage switch leukaemia are scarcely found in the literature. Stass et al (1984) reported an achievement of remission with treatment adjusted to the phenotype evident at lineage switch after initial lineage-specific chemotherapy. Only three of our eight lineage switch patients, all carrying a trisomy 8, are still alive ( Figure S1B).…”

Section: Treatment and Outcomementioning

confidence: 99%

Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations

et al. 2010

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SummaryAcute leukaemias of ambiguous lineage (ALAL) represent a rare type of leukaemia, expressing both myeloid and lymphoid markers. This study retrospectively analyzed data from 92 children (biphenotypic n = 78, bilineal n = 6, lineage switch n = 8) with ALAL registered in the Berlin-Frankfürt-Münster (BFM) acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) studies between 1998 and 2006 (2AE4% of all cases with acute leukaemia). Our cohort of ALAL patients was characterized by comparatively high median age (8AE9 years), high median white blood cell count (14AE9 · 10 9 /l), as well as frequent hyperleucocytosis (18AE5%) and central nervous system involvement (24AE1%). The most frequent cytogenetic abnormalities were ETV6/RUNX1 fusion (16%) and trisomy 8 (14AE6%). Complete remission rate was significantly lower than in ALL-BFM patients (91AE8% vs. 99AE1%, P < 0AE001), but comparable to AML-BFM patients (87AE9%). Event-free survival (EFS) and overall survival (OS) of ALAL patients were low, at 62 ± 5%. 5-year probability of EFS was significantly worse than in ALL patients (80 ± 1%, P < 0AE001), but better than for AML patients (49 ± 2%, P = 0AE027). Our data suggest that an intensive therapy regimen including stem cell transplantation may be favourable for bilineal or lineage switch cases, whereas patients with ETV6/RUNX1 fusion, lymphoid morphology and patients with expression of cyCD22 and cyCD79a should be treated with an ALL-directed therapy.

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Lineage switch in acute leukemia

Cited by 204 publications

References 23 publications

Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Characterization of myeloid leukemias with monoclonal antibodies 3C5 and MY9

Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations

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