This work describes a Drosophila model of acute myeloid leukemia related to misexpression of the human gene MLF1. MLF1 is thought to encode a transcriptional regulator and is known to play a role in the determination of hematopoietic cells. Translocations between MLF1 and nucleophosmin (NPM1) have been associated with myelodysplastic syndrome and acute myeloid leukemia. There is a single gene orthologous to MLF1 in Drosophila, Dmel\Mlf, for which loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Mlf is also orthologous to a second human gene, MLF2.
UAS constructs of the wild-type human genes, Hsap\MLF1 and Hsap\MLF2, have been introduced into flies. Expression of Hsap\MLF1 results in heterologous rescue (functional complementation) of several Dmel\Mlf loss-of-function phenotypes, including the decrease in embryonic crystal cell numbers, and adult bristle and wing phenotypes.
In Drosophila, the RUNX family transcription factor lozenge (Dmel\lz) is specifically expressed in a class of hemocytes called crystal cells; it is required for the development of this blood cell lineage. Dmel\Mlf has been shown (acting in concert with DnaJ-1) to stabilize lz and to promote its accumulation in the developing crystal cells.
Animals homozygous for loss-of-function alleles of Dmel\Mlf typically die during the embryonic stage; a reduction in the number of crystal cells is observed. A small percentage of homozygous animals survive to adulthood; they exhibit very mild bristle and wing phenotypes. Genetic and physical interactions have been described for Dmel\Mlf (including with lz and DnaJ-1); see below and in the Mlf gene report.
[updated Jan. 2020 by FlyBase; FBrf0222196]
Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults; it is uncommon under age 40. (Most childhood leukemias are acute lymphocytic leukemia, ALL). AML affects myeloid cells, resulting in an abundance of abnormal immature cells within the blood-cell-producing bone marrow; normal hematopoietic processes become increasingly compromised. Persons with AML are more likely to have infections and have an increased risk of bleeding as the numbers of healthy blood cells decrease. [from MedlinePlus; https://www.nlm.nih.gov/medlineplus/ency/article/000542.htm ]
MLF1 is thought to encode a transcriptional regulator; it plays a role in the determination of hematopoietic cells. [Gene Cards, MLF1; 2020.01.21]
Many to one (2 human to 1 Drosophila); the second human gene is MLF2.
