Issue Highlights – May 2019

MIXED LINEAGE ACUTE LEUKEMIA Mixed lineage acute leukemia (MPAL) is a rare subtype of acute leukemia defined on cytomorphological and particularly, on immunophenotypic grounds based on co-expression of markers of two distinct (e.g. myeloid and B-lymphoid) lineages in either one (biphenotypic MPAL) or ≥ two distinct blast cell populations (bi-lineal MPAL). Following previous reports of rare hybrid, biphenotypic, bilineal and ambiguous leukemias, MPAL was first recognized in the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, as a unique poor-prognosis subtype of acute leukemia, in 2008 (1). In this classification, WHO further recognized the high biological heterogeneity of MPAL and subdivided it into three disease categories defined on genetic grounds. Since then, flow cytometry-based immunophenotypic criteria have been a cornerstone in the diagnosis of MPAL. In 2017 however, WHO diagnostic criteria for MPAL were revised, modified and to a certain extent simplified, while MPAL subclassification criteria remained unchanged (2). In the last decade, important contributions and (some) advances have been made in the field of MPAL and the understanding of this rare subtype of acute leukemia, which are scattered across a few hundred manuscripts in the literature including a few case reports and an editorial comment in Cytometry B (3–6). In this issue, Porwit and Bene (7), two authors who have most contributed to the definition of MPAL and the advancement of the knowledge about this unique subtype of acute leukemia (1,2,8,9), provide recommendations for correct immunophenotypic diagnosis of MPAL, together with a comprehensive overview of other investigations required for definitive diagnosis of MPAL. At the same time they offer the reader an up-to-date review of the most recent contributions in the field, particularly as regards the cytogenetic and molecular alterations described so far in MPAL, its great biological heterogeneity, and the potential role of early stem cell transplantation on improving outcome of MPAL patients (7). MULTIPLE MYELOMA Until the early 1990s flow cytometry was considered of limited value in multiple myeloma (MM). However, introduction of CD38 as a plasma cell (PC) gating marker (10), together with the development of multicolour flow cytometry demonstrated the great potential of flow-based immunophenotyping in distinguishing between normal and aberrant (clonal) PC, and further characterizing the latter cells (11–14). In recent years, immunophenotypic monitoring of minimal residual disease (MRD) after therapy using high-sensitive flow cytometry (15,16) has become recognized as one of the most powerful parameters to evaluate response to therapy in bone marrow, and to predict patient outcome (17,18). As a consequence, flow-MRD has become part of the treatment-decision making process in many recent clinical trials (19). Here, Rossi et al. (20) used an in-house developed six-color flow cytometry assay to compare response to therapy in patients undergoing single vs double transplant. Their results show the potential benefit of a double transplant based on its association with better clearance of myeloma cells in bone marrow. In order to be able to translate these results into routine practice at distinct laboratories, standardization is mandatory (19). This is clearly highlighted in this issue in the work presented by Scott et al. (21), who report on the high sensitivity and good linearity observed in an International Inter-Laboratory Study based on dilutional series of MM samples.