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Related Experiment Video

Updated: Jun 28, 2026

Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm

Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm

Published on: December 22, 2016

Covert preleukemia driven by MLL gene fusion.

Jan Zuna¹, Tatiana Burjanivova, Ester Mejstrikova

¹Department of Paediatric Haematology and Oncology, Childhood Leukaemia Investigation Prague, Charles University Prague, 2nd Medical School, Czech Republic. jan.zuna@lfmotol.cuni.cz

Genes, Chromosomes & Cancer

|October 22, 2008

Summary

The study reveals a hidden preleukemic phase in MLL-rearranged leukemia, where a dominant clone exists before overt disease. A subsequent genetic gain on 19q13.32 triggered the progression to secondary acute lymphoblastic leukemia (sALL).

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Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

Area of Science:

Hematology
Cancer Biology
Genetics

Background:

Acute leukemia pathogenesis is often a multi-step process, with the 'second hit' genetic event remaining poorly understood, particularly in cases involving MLL gene rearrangements.
Understanding the sequence of genetic events is crucial for deciphering leukemogenesis and developing targeted therapies.

Observation:

A protracted preleukemic phase was identified in secondary acute lymphoblastic leukemia (sALL) with MLL rearrangement, characterized by a dominant MLL/FOXO3A clone.
This preleukemic clone exhibited intact myeloid differentiation and was present in up to 90% of bone marrow cells over a year before sALL diagnosis.
No overt leukemic blasts were detected in the bone marrow during this preleukemic phase.

Findings:

The MLL/FOXO3A fusion likely originated in a multipotent progenitor cell.
A significant genetic abnormality, a 10 Mb gain on chromosome 19q13.32, was identified in the sALL samples but was absent in the preceding preleukemic specimens.
This gain on 19q13.32 is proposed as the critical 'second hit' that precipitated the transformation to overt lymphoblastic leukemia.

Implications:

These findings elucidate the dynamic process of leukemogenesis in MLL-rearranged secondary leukemias.
Identifying the specific genetic alterations driving leukemic progression can inform diagnostic strategies and therapeutic interventions.
This research provides a deeper understanding of the clonal evolution and genetic landscape underlying complex leukemic transformations.