Page 1039 - Hematology_ Basic Principles and Practice ( PDFDrive )

922 Part VII Hematologic Malignancies

SDF1/CXCL12
FLT3L FLT3L
Stromal
C-KIT fibroblast
FLT3
ITD
RAS P13K
JAK
TKD TKD RAF
SHC SHP PTEN PIP3
JAK2 SHIP GRB2
PDK1
MEK isocitrate
STAT STAT IDH1/2 AKT1 HDM2

ERK
KG mTOR P53
mutIDH1/2
2HG ARF
P14
NPM1
Spliceosome

TET2 NPM1

CBFB RUNX1 HDAC
ETO DNMT3L
HMT
PML
DNMT3A
RARA
Ac
OH N
CEBPA
CH 3 CH 3
H 4
H 2A
ASXL1
H 3 CH 3
GATA2 H 2B EZH2
NSD1 NUP98
MLL
Cohesin DOT1L
complex AF9
Fig. 58.3 COMMONLY ALTERED CELLULAR PATHWAYS IN ADULT ACUTE MYELOID LEUKE-
MIA. Mutations in acute myeloid leukemia commonly affect pathways related to cell signaling, differentiation,
secondary modifications of DNA, and tumor suppressor genes. Collectively, these lesions interfere with self-
renewal, differentiation, and survival pathways. Ac, acetyl; AF9, ALL1-fused gene from chromosome 9 protein;
α-KG, α-ketoglutarate; ARF, ADP-ribosylation factor; AKT1, AKT serine/threonine kinase 1; ASXL1, addi-
tional sex Combs-like 1; CBFB, core binding factor b; CEBPA, CCAAT/enhancer binding protein-alpha; CH 3 ,
methyl; CXCL12, CXC-chemokine ligand 12; DNMT3A, DNA methyltransferase 3A; DNMT3L, DNA
methyltransferase 3 like; DOTIL, disruption of telomeric silencing 1-like; ERK, Extracellular signal-related
kinase; ETO, eight twenty one or RUNX1T1; EZH2, Enhancer of zeste homolog 2; FLT3L, FMS-like tyrosine
kinase-3 ligand; GATA1, GATA binding protein 1; GRB2, growth factor receptor–bound protein 2; H, histone;
HDAC, histone deacetylase; HDM2, human homolog of double minute 2, P53-binding protein; HMT,
histone methyltransferase; IDH1/2, isocitrate dehydrogenase-1/2; ITD, internal tandem duplication: JAK,
Janus-activated kinase; MEK, mitogen-activated protein kinase kinase; MLL, mixed lineage leukemia; mTOR,
mammalian target of rapamycin; N, nitrogen; NPMI, nucleophosmin; NSD1, nuclear receptor binding SET
domain protein 1; Nup98, nucleoporin 98; OH, hydroxyl; P14 ARF , cyclin-dependent kinase inhibitor 2A; p53,
tumor protein p53; RARA, retinoic acid receptor alpha; PDK1, phosphoinositide-dependent kinase-1; PI3K,
phosphatidylinositol 3-kinase; PIP3, phosphoinositide-3,4,5-trisphosphate; PML, promyelocytic leukemia;
PTEN, phosphatase and tensin homolog; RAF, RAF kinase family; RAS, RAS family kinase; RUNX1, runt-
related transcription factor 1; SDF-1, stromal cell–derived factor 1; SHC, Src Homology 2 Domain-Containing;
SHIP, SH 2 -containing inositol phosphatase; SHP, small heterodimer partner; STAT, signal transducer and
activator of transcription; TET2, TET oncogene family member 2; TKD, tyrosine kinase domain.