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Table 1 Characterized RBPs in MLL-AF9 and MLL-AF4 Leukemia

From: RNA binding proteins in MLL-rearranged leukemia

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

[51, 52]

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

[55, 56]

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

[72, 73]

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

[86, 87]

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

[95, 96]

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

[108, 112, 113]

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

[120, 121]

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

[135, 136, 137, 139]

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

[143, 58]