INTRODUCTION
Philadelphia chromosome - like acute lymphoblastic leukemia (Ph-like
ALL) is defined by a gene expression profile similar to BCR::ABL1ALL.1 and associated with chemotherapy resistance and
high risk of relapse.2 The four major subgroups of
Ph-like ALL consist of CRLF2 rearrangements, ABL -class
fusions, EPOR rearrangements, and JAK2rearrangements.3 In addition, somatic NTRK3 and RAS
signaling pathway mutations (IL-7R, KRAS, NRAS) have been identified in
a subset of Ph-like ALL.4
Histiocytic disorders are characterized by aberrant accumulation of
phagocytes frequently with activating somatic mutations in RAS-MAPK
pathway genes.5 Juvenile Xanthogranuloma (JXG)
typically presents as a benign self-resolving non-Langerhans-cell
histiocytic cutaneous proliferation . Clinical behavior and histology of
disseminated JXG overlap with malignant histiocytosis (or histiocytic
sarcoma) that can arise as a primary neoplasm or be associated with
precursor hematopoietic malignancies, such as juvenile myelomonocytic
and acute lymphoblastic leukemia.5-11 Secondary
histiocytic neoplasms and their associated hematologic neoplasms share
common genetic aberrations suggesting clonal divergence.10
Here we report the first known case of a pediatric patient with
refractory Ph-like B-ALL complicated by disseminated JXG and
hemophagocytic lymphohistiocytosis (HLH) treated with targeted therapy.
This case provides unique insight into the drivers of both Ph-like B-ALL
and JXG and illustrates novel use of a targeted MEK inhibitor.