To the Editor:
Mixed-phenotype acute leukemia (MPAL) is a rare, heterogeneous group of
leukemia that comprises admixture of myeloid and lymphoid blasts
(bilineal) or a single blast population co-expressing lymphoid and
myeloid markers (biphenotypic). The accurate diagnosis relies on the
immunophenotype of flow cytometric or immunostaining
findings.1-3 European Group of Immunological
Characterization of Leukemia (EGIL) was released in 1990s to establish
guidelines for the characterization of acute leukemia based on marker
expression,2 and the World Health Organization (WHO)
classification also acknowledges lineage-specific antibodies and genetic
markers.2 In brief, the assignment of myeloid lineage
depends on the expression of Myeloperoxidase (MPO); the assignment of
monocytic differentiation depends on at least 2 of the following:
Nonspecific Esterase, CD11c, CD14, CD64 or Lysosome; the assignment of
B-lineage depends on CD19 and more than 1 or 2 strong expression of
CD79a, cytoplasmic CD22 or CD10; the assignment of T-lineage depends on
strong cytoplasmic CD3 (strong is equal to brighter than the normal T
cells) or surface CD3 expression.1
Recent genetic studies reveal recurrent aberrations in MPAL, which have
been integrated in the classification of MPAL with BCR::ABL1fusion, KMT2A rearrangement, ZNF384 rearrangement, andBCL11B rearrangement.1 Within these genetic
aberrations, BCL11B rearrangement is particularly interesting.
Inactivating mutations of BCL11B have been identified in up to
16% of T-acute lymphoblastic leukemia (T-ALL), indicating its likely
role of tumor-suppressor gene for T-ALL.4,5 However,
novel BCL11B rearrangements have been identified in MPAL, early
T-precursor-ALL, and in poorly differentiated AML with aberrant T-cell
antigen expression.6-10
The complex phenotype of MPAL creates not just a diagnostic challenge,
but challenges in determining and initiating optimal
therapy.11 Lack of prospective trials and varying
classification systems leads to inability to define standard therapy. A
recent retrospective study by an MPAL cohort from the Children’s
Oncology Group (COG), suggests that ALL chemotherapy without HSCT may be
the preferred initial therapy for pediatric MPAL.12Ongoing efforts are underway within COG to prospectively evaluate the
use of high risk ALL therapy in MPAL. Here we report a diagnostically
challenging T/My MPAL patient with BCL11B copy gain.