MKPL-1
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The MKPL-1 is a human leukemic cell line. The cells are isolated from the peripheral blood of a 36-year-old male patient with acute megakaryoblastic leukemia (AMKL), a rare and often aggressive subtype of acute myeloid leukemia (AML). The MKPL-1 cell line, as such, provides an in vitro model for AMKL. The MKPL-1 cells, as cultured in vitro, display a blast-like morphology and show growth in suspension as single cells or small aggregates. The doubling time is approximately 24-48 hours. A key morphologic and functional feature of this cell line is the ability of the cells to demonstrate features of megakaryocytic differentiation upon treatment with specific pharmacological stimuli, such as phorbol esters (PMA). This can be assessed both by morphological changes (e.g. expansion of cytoplasm, protrusions) and an increased expression of megakaryocytic surface markers such as CD41, and CD61.
Functionally, MKPL-1 is an important model to study the pathophysiology of AMKL in particular and to do research involving aberrant megakaryopoiesis and leukemogenesis. Its main applications are for drug screens for novel anti-leukemic compounds, drug resistance studies, as well as differentiation therapy approaches. The cell line has also been used for molecular research looking at the role of specific genetic alterations in leukemogenesis, such as the CBFA2T3-GLIS2 fusion oncogene which is often associated with poor prognosis in pediatric AMKL.
Chromosomal and Genomic Analyses of the Gene Loci for IRX1, IRX3, and IRX5 in AML
Homeobox genes encode transcription factors crucial for development, including hematopoiesis. Recently, the lymphoid TALE-code was constructed, detailing TALE homeobox gene expression in early hematopoiesis. Building on the lymphoid TALE-code, Nagel et al. constructed the myeloid TALE-code to cover the entire hematopoietic system. Then, they investigated the role of TALE homeobox genes, particularly IRX1, IRX3, and IRX5, in myeloid differentiation and acute myeloid leukemia (AML).
To determine if chromosomal rearrangements activate IRX genes in AML, they reviewed published karyotypes of relevant cell lines and identified i(5)(p10) in OCI-AML3 and MKPL-1 and del(16)(q13q23) in MEGAL as potential activating alterations. They then performed genomic profiling on AML cell lines CMK, M-07e, MKPL-1, UT-7, MEGAL, and OCI-AML3, focusing on chromosomes 5 and 16 (Fig. 1). IRX1 (5p15) is duplicated in OCI-AML3 and MKPL-1, consistent with isochromosome formation for the short arm. However, OCI-AML3 is IRX1-negative, suggesting this duplication does not activate IRX1. In contrast, IRX3 and IRX5 at 16q12 are significantly amplified in MEGAL, with several amplicons covering the entire long arm of chromosome 16. RNA-seq data for the nearby FTO locus, which regulates IRX3/IRX5 activity, showed enhanced expression in MEGAL. This genomic amplification likely drives IRX3/IRX5 activation in MEGAL. RT-PCR confirmed no CBFb-MYH11 fusion gene formation via inv(16)(p13q22) in MEGAL.

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