Contributions
Abstract: PB1661
Type: Publication Only
Background
Mixed-phenotype acute leukemias (MPALs) are rare leukemias often presenting with difficulties of classification and treatment. According to the revised WHO 2016 criteria, the identification of their myeloid component still relies on the expression of MPO, yet a new subgroup of otherwise typical B-ALLs with low levels of MPO has been recognized of unknown clinical significance up to now.
Aims
This study is a meta-analysis of our cohort of MPALs, the recent WHO revision taken in account.
Methods
In a total of 700 de novo adult acute leukemias 24 (3.4%) were classified as MPAL according to WHO 2008 by multi-color flow cytometry (FC), using CDs 19,79a, 10, 20 as B-lineage markers, CDs 3, 2, 5, 7 as T-lineage and cytoplasmicMPO (cut-off 10%), c13, s13, s33, 117 as myeloid markers. Cytochemical MPO (cut-off 3%) was also evaluated in all cases. Karyotype and FISH defined genetic groups.
Results
16/24 MPALs were B+M and 8/24 T+M. Discordance of cytochemistry and FC for MPO determination was found at 10/24 MPAL cases (41.7%) , that is 9 MPO-positive cases identified only by cytochemistry and 1 only by FC. All discordant cases had isolated low MPO expression (4-20% positive blast cells) and an immunophenotype of Pro-B (5), pre-B (1), common B (1), pre-T (2) and mature T(1) ALL, without any other markers of myeloid differentiation. Interestingly, 3 of these cases clearly co-expressed MPO and lymphoid markers at relapse by FC as well. According to cytogenetic data, 50% of the B+M MPALs were BCR/ABL- or MLL- associated and all but one of the “MPO- discordant” cases belonged to these genetic groups.
Conclusion
The determination of an isolated low-intesity MPO in MPALs may be challenging, due to the lack of an established threshold for FC and to technical reasons. The WHO 2016 revision draws attention to a group of acute leukemias with B-cell phenotype and low MPO expression of unknown clinical significance. In this study almost 50% of our B+M MPAL cases, all but one being MLL- or BCR/ABL- associated, matched this description and it was the combined cytochemical and FC approach for MPO that disclosed their myeloid component, as well as at a few T-ALLs. In our experience this combination is most helpful for the better identification of these rare MPALs with isolated low MPO.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Cytometry, Leukemia, Mixed lineage leukemia
Abstract: PB1661
Type: Publication Only
Background
Mixed-phenotype acute leukemias (MPALs) are rare leukemias often presenting with difficulties of classification and treatment. According to the revised WHO 2016 criteria, the identification of their myeloid component still relies on the expression of MPO, yet a new subgroup of otherwise typical B-ALLs with low levels of MPO has been recognized of unknown clinical significance up to now.
Aims
This study is a meta-analysis of our cohort of MPALs, the recent WHO revision taken in account.
Methods
In a total of 700 de novo adult acute leukemias 24 (3.4%) were classified as MPAL according to WHO 2008 by multi-color flow cytometry (FC), using CDs 19,79a, 10, 20 as B-lineage markers, CDs 3, 2, 5, 7 as T-lineage and cytoplasmicMPO (cut-off 10%), c13, s13, s33, 117 as myeloid markers. Cytochemical MPO (cut-off 3%) was also evaluated in all cases. Karyotype and FISH defined genetic groups.
Results
16/24 MPALs were B+M and 8/24 T+M. Discordance of cytochemistry and FC for MPO determination was found at 10/24 MPAL cases (41.7%) , that is 9 MPO-positive cases identified only by cytochemistry and 1 only by FC. All discordant cases had isolated low MPO expression (4-20% positive blast cells) and an immunophenotype of Pro-B (5), pre-B (1), common B (1), pre-T (2) and mature T(1) ALL, without any other markers of myeloid differentiation. Interestingly, 3 of these cases clearly co-expressed MPO and lymphoid markers at relapse by FC as well. According to cytogenetic data, 50% of the B+M MPALs were BCR/ABL- or MLL- associated and all but one of the “MPO- discordant” cases belonged to these genetic groups.
Conclusion
The determination of an isolated low-intesity MPO in MPALs may be challenging, due to the lack of an established threshold for FC and to technical reasons. The WHO 2016 revision draws attention to a group of acute leukemias with B-cell phenotype and low MPO expression of unknown clinical significance. In this study almost 50% of our B+M MPAL cases, all but one being MLL- or BCR/ABL- associated, matched this description and it was the combined cytochemical and FC approach for MPO that disclosed their myeloid component, as well as at a few T-ALLs. In our experience this combination is most helpful for the better identification of these rare MPALs with isolated low MPO.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Cytometry, Leukemia, Mixed lineage leukemia