# Selumetinib as an Effective Therapy of Histiocytic Sarcoma Evolving From a B‐Cell Acute Lymphoblastic Leukaemia

## TL;DR

A child with B-cell leukemia developed histiocytic sarcoma, which responded to selumetinib due to a genetic mutation.

## Contribution

Demonstrates transdifferentiation in cancer and the effectiveness of MEK inhibition in MAPK-driven histiocytic sarcoma.

## Key findings

- HS evolved from B-ALL with shared genetic markers suggesting transdifferentiation.
- Selumetinib treatment led to rapid response in MAP2K1-mutated histiocytic sarcoma.
- PAX5 alterations were linked to lineage plasticity in the tumor.

## Abstract

Histiocytic sarcoma (HS) is a rare neoplasm derived from non‐Langerhans histiocytic cells, exceptionally arising from B‐ALL.

We present the case of a child with high‐risk B‐ALL with PAX5 P80R mutation.

Despite initial remission, a chemoresistant paravertebral mass was identified as HS. A shared IGK/TCRB rearrangements and PAX5 alterations between the leukaemic and histiocytic clones suggested transdifferentiation driven by PAX5. A somatic MAP2K1 mutation in the HS component prompted selumetinib treatment, leading to a rapid response.

This case underscores the role of PAX5 in lineage plasticity and highlights the potential of targeted MEK inhibition in MAPK‐driven HS arising from B‐ALL.

The authors have confirmed clinical trial registration is not needed for this submission