RBP | MLL FP | Type of leukemia | Mechanism | Function | Characterization | Refs. |
---|---|---|---|---|---|---|
METTL3 | MLL-AF9 | AML | RNA modification | m6A writer | Human primary AML cells, Human MOLM-13 cell line, MLL-AF9 Flt3-ITD mouse model, CRISPR dropout screen | |
METTL14 | MLL-AF9 | AML | RNA modification | m6A writer | Human primary AML cells, Human MM6 cell line, MLL-AF9 Mettl14 CKO mouse model | [53] |
FTO | MLL-AF9 | AML | RNA modification | m6A eraser | Human primary AML cells, Human MONOMAC-6 and MV4-11 cell lines, MLL-AF9 Fto knockdown and heterzygous knockout mouse model | [54] |
ALKBH5 | MLL-AF9, MLL-AF4 | AML | RNA modification | m6A eraser | Human primary AML cells, Human MONOMAC-6, NOMO1 MOLM-13, THP-1, MV4-11 cell lines, MLL-AF9 Alkbh5 CKO mouse model | |
YTHDF2 | MLL-AF9 | AML | RNA modification | m6A reader | Human primary AML cells, Human THP-1 cell line, Ythdf2 CKO Hoxa9 Meis1 mouse model | [57] |
METTL1 | MLL-AF9 | AML | RNA modification | m7G writer | Human primary AML cells, Human MOLM-13 and THP-1 cell lines, MLL-AF9/Flt3ITD/+ deletion mouse model, MLL-AF9 AML xenograft mouse model | [63] |
ADAR1 | MLL-AF9 | AML | RNA editing | A-to-I editing | Human primary AML cells, Human THP-1 cell line, MLL-AF9 Adar1 CKO mouse model | |
RBM39 | MLL-AF9 | AML | Alternative splicing | Splicing factor | RBD CRISPR/Cas9 screen, Human primary AML cells, Human MOLM-13 and THP-1 cell lines, MLL-AF9 NrasG12D mouse model | [81] |
DCPS | MLL-AF9, MLL-AF4 | AML | Alternative splicing | 5′ cap binding enzyme | Human MOLM-13, THP-1, and MV4-11 cell lines, Genome-wide CRISPR/Cas9 screen using MLL/AF9-Cas9 mouse model, PDX AML models | [84] |
MBNL1 | MLL-AF9, MLL-AF4 | ALL, AML | Alternative splicing | Splicing, mRNA decay | Human primary MLL-r leukemia cells, Human THP-1, RS4;11, MOLM13, SEM and MV4-11 cell lines, MLL-Af4 mouse model, MLL-AF9 PDX with Mbnl1 knockdown mouse model, MLL-AF9 Mbnl1 KO mouse model | |
DROSHA | MLL-AF9, MLL-AF4 | AML, ALL | Primary miR processing | miR biogenesis | Human primary AML cells, Human SEMK2, PER377, MV4-11 cell line, MllPTD/wt/Flt3ITD/ITD mouse model | |
NCL | MLL-AF9, MLL-AF4 | AML | mRNA stability and 3′UTR association | Ribosome biogenesis, miR biogenesis | Human primary AML and ALL cells, Human MOLM-13 and MV4-11 cell lines, Cell-line MLL-AF9 xenograft NCL knockdown mouse model | |
ZFP36L1 | MLL-AF9 | AML | mRNA stability and 3′UTR association | MZ B cell maintenance, thymopoiesis | Human primary MLL-r AML cells, Human THP-1 cell line | [114] |
LIN28B | MLL-AF9 | AML | Multiple mechanisms of action | Embryonic stem cell pluripotency, self-renewal, fetal lymphopoiesis, miR biogenesis | Human MLL-r AML cells, Human THP-1 cell line, AML xenograft mouse model, MLL-AF9 AML mouse model | |
MSI2 | MLL-AF9 | AML | Multiple mechanisms of action | Self-renewal and pluripotency of embryonic stem cells, regulation of HSCs | Human primary AML cells, Human NOMO-1 and THP-1 cell lines, MLL-AF9 AML Msi2 conditional knockout mouse model | |
SYNCRIP | MLL-AF9 | AML | Multiple mechanisms of action | Regulation of transcripts involved in myeloid leukemia stem cells | Human primary AML cells, Human NOMO-1, MOLM-13, and THP-1 cell lines, MLL-AF9 leukemia in vivo shRNA screen, MLL-AF9 AML Syncrip KO mouse | [138] |
IGF2BP3 | MLL-AF4 | ALL | Multiple mechanisms of action | Cell migration, survival, differentiation and stem cell renewal | Human primary ALL cells, Human RS4;11 and SEM cell lines, IGF2BP3 enforced expression mouse model, MLL-Af4 Igf2bp3 KO leukemia model |