A scientific treatment approach for acute mast cell leukemia: using a strategy based on next-generation sequencing data.
BACKGROUND
Mast cell leukemia (MCL) is the most aggressive form of systemic mastocytosis disorders. Owing to its rarity, neither pathogenesis nor standard treatment is established for this orphan disease. Hence, we tried to treat a patient with MCL based on the exome and transcriptome sequencing results of the patient's own DNA and RNA.


METHODS
First, tumor DNA and RNA were extracted from bone marrow at the time of diagnosis. Germline DNA was extracted from the patient's saliva 45 days after induction chemotherapy and used as a control. Then, we performed whole-exome sequencing (WES) using the DNA and whole transcriptome sequencing (WTS) using the RNA. Single nucleotide variants (SNVs) were called using MuTect and GATK. Samtools, FusionMap, and Gene Set Enrichment Analysis were utilized to analyze WTS results.


RESULTS
WES and WTS results revealed mutation in KIT S476I. Fusion analysis was performed using WTS data, which suggested a possible RARα-B2M fusion. When RNA expression analysis was performed using WTS data, upregulation of PIK3/AKT pathway, downstream of KIT and mTOR, was observed. Based on our WES and WTS results, we first administered all-trans retinoic acid, then dasatinib, and finally, an mTOR inhibitor.


CONCLUSIONS
We present a case of orphan disease where we used a targeted approach using WES and WTS data of the patient. Even though our treatment was not successful, use of our approach warrants further validation.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Jeonghwan
J
Youk
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Youngil
Y
Koh
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Ji-Won
JW
Kim
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Dae-Yoon
DY
Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Hyunkyung
H
Park
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Woo June
WJ
Jung
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Kwang-Sung
KS
Ahn
Bioinformatics Group, Platform Development Center, CSP R&D, Samsung SDS, Seoul, Korea.
Hongseok
H
Yun
Bioinformatics Group, Platform Development Center, CSP R&D, Samsung SDS, Seoul, Korea.
Inho
I
Park
Bioinformatics Group, Platform Development Center, CSP R&D, Samsung SDS, Seoul, Korea.
Choong-Hyun
CH
Sun
Bioinformatics Group, Platform Development Center, CSP R&D, Samsung SDS, Seoul, Korea.
Seungmook
S
Lee
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Sung-Soo
SS
Yoon
C-kit; Individualized medicine; Leukemia; Mast cell