Issue Highlights - March 2019.

Abstract

This issue features, among others, two reviews and four original manuscripts in the field of clinical cytometry, all of them in the area of leukemia/lymphoma immunophenotyping. These may be summarized as follows: Jevremovic and colleagues reviewed the position of flow cytometry in the diagnosis, prognosis and follow-up of T- and NK-cell lymphoproliferations 1. The diagnosis of these entities is generally based on the demonstration of immunophenotypic abnormalities and demonstration of clonality. The latter studies involve V-beta T-cell receptor repertoire analysis and killer immunoglobulin like receptors (KIR). In this context it is important to realize that a T-cell clone does not need to be synonymous with “malignancy” but could also reflect the transient clonal proliferation of “reactive” T cells. Among the mature T-cell lymphoproliferative disorders, T-cell large granular lymphocytic leukemia (T-LGLL), anaplastic large T-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), mycosis fungoides or Sezary syndrome (MF/SS), T-cell prolymphocytic leukemia (T-PLL), hepatosplenic T-cell lymphoma (HSTCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) are distinguished. Within the NK-cell disorders, chronic lymphoproliferative disorder of NK cells (CLPD-NKs), extranodal NL/T-cell lymphoma, nasal type, aggressive NL-cell leukemia/lymphoma and NK-cell enteropathy are defined. Nowadays, flow cytometry is a sensitive and specific approach to detect T and NK-cell neoplasms but requires a thorough knowledge of the normal T-cell and NK-cell immune spectrum. Jan W. Gratama, Deputy Editor [Color figure can be viewed at wileyonlinelibrary.com] CD123, the alpha chain of IL3 receptor, is expressed in variable intensities on human leukocytes; the strongest expression is seen on plasmacytoid dendritic cells and basophils, whilst the marker is absent on nucleated red blood cells; a range of intermediate expression levels are seen on T cells, mature B cells, granulocytes and eosinophils. CD123 is expressed on AML blasts and most B-cell precursor ALL blasts whilst it is negative on most T-ALL blasts. The teams of the Laboratory for Medical Immunology at Erasmus MC (Rotterdam, Netherlands) in collaboration with the Dutch Childhood Oncology Group (The Hague, Netherlands) set out to study CD123 expression levels in 846 patients with acute leukemia in comparison to normal cell populations obtained in 1,252 unique bone marrow and peripheral blood samples 6. Immunophenotyping was performed using standardized procedures as developed by the EuroFlow collaborative project 7. Whilst published information on this topic was relatively scarce and difficult to compare due to different methodologies, Bras and colleagues confirmed most observations as they extensively document in this report 6. Importantly, they observed that in paired B-cell precursor ALL, CD123 expression was considerably higher at relapse than at initial diagnosis, whilst in AML, the leukemic stem cells (CD34pos, CD38neg fraction of tumor cells) expressed similar CD123 levels as the remainder of AML blasts. These observations make CD123 an interesting target for antibody-targeted therapy 8. Early positive minimal residual disease (MRD) is a strong predictor of response to treatment in ALL and AML. In an observational study of 125 children with B-cell precursor ALL, Loosveld and colleagues 9 investigated the prognostic value of flow cytometric assessment of MRD in peripheral blood on days 8 and 15 after start of cytoreductive therapy, compared to day 35 MRD on bone marrow using molecular techniques. Children with detectable PB MRD on day 15 and negative day 35 BM results had lower disease-free survival at 4 years follow-up, indicating the prognostic potential of this less invasive, blood-based procedure early after start of therapy as compared to conventional bone marrow studies. Mora and colleagues 10 studied 120 consecutive patients with chronic B-lymphoproliferations (81 within the CLL spectrum and 39 with other monoclonal B-cell disorders) to establish whether CD200, a member of the Ig receptors membrane proteins superfamily, would have added value to the immunological scoring system already developed by Matutes et al. 11. CD200 had already been suggested to be rather specific for B-CLL in earlier studies. This study confirmed the value of CD200 as diagnostic marker and revealed that it's addition to the Matutes score increased the accuracy of that ranking algorithm. Beke Debreceni et al. 12 analyzed the regulation of expression of the adhesion receptor L-selectin (CD62L) in a cohort of untreated patients with B-CLL. Expression of surface-bound CD62L and tumor necrosis factor alpha-converting enzyme (TACE), as well as total phosphatase and protein phosphatase-2A activities, were lower on B-CLL than on normal B cells whilst the reverse was true for soluble CD62L and phosphorylated mitogen-activated protein kinase (pp38MAPK). In separate in vitro experiments confirmed that a phosphatase inhibitor (calyculin A) could reduce the effect of pp38MAPK inhibitor on CD62L shedding. The authors concluded that the reduction of phosphatase activity in B-CLL has resulted in a downstream signaling cascade with subsequent reduction of surface-bound CD62L which is mediated by enhanced phosphorylation of p38MAPK and reduced TACE expression. Jan W. Gratama, Deputy Editor Email: j.w.gratama@erasmusmc.nl