Triple-negative Thrombocythemia and Subsequent Acute Lymphoblastic Leukemia with Additional Somatic Mutations

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Triple-negative essential thrombocythemia (ET) is characterized by the absence of JAK2, CALR, and MPL mutations.
• Transformation to myeloid leukemia is known, but B-acute lymphoblastic leukemia (B-ALL) is exceptionally rare in ET patients.

Purpose of the Study:

• To report a rare case of B-ALL developing during the course of triple-negative ET.
• To investigate the potential genetic drivers of this transformation using whole exome sequencing.

Main Methods:

• Case report of a patient with triple-negative ET who developed B-ALL.
• Whole exome sequencing (WES) was performed on both ET and B-ALL samples.
• Comparative analysis of somatic mutations between ET and B-ALL stages.

Main Results:

• The patient was diagnosed with B-ALL during triple-negative ET.
• Cytoreduction was necessary post-chemotherapy due to hyperleukocytosis during bone marrow recovery.
• WES identified 17 somatic mutations: 9 shared between ET and B-ALL, and 8 unique to B-ALL.

Conclusions:

• The 8 B-ALL-specific mutations are potential candidates driving the transformation from triple-negative ET to B-ALL.
• This case highlights the importance of comprehensive genetic analysis in understanding rare leukemic transformations.