Mutation induces leukemia in mouse model.

Table 1. Mutations in the PI3K/PKB pathway.

#### **3.1.3 Activating mutations upstream of PI3K/PKB signaling pathway**

The PI3K/PKB signaling module is an important mediator of cytokine signals. In hematological malignancies, mutations in cytokine receptors have been described to affect

mutation has only been detected in one pediatric T-ALL patient (Gutierrez et al., 2009). To

E542K Activation # Helical domain p110α Horn , 2008 H1047R Activation # Kinase domain p110α Horn , 2008 PIK3CA Activation T-ALL Catalytic subunit PI3K Gutierrez , 2009 PIK3R1 Deletion T-ALL Regulatory subunit PI3K Gutierrez , 2009

Dysruption T-ALL Sequence alterations in exon 7 Gutierrez , 2009

ALL Juxtamembrane (JM) domain

autoinhibition AML Juxtamembrane (JM) domain Reviewed by

Activation loop (AL) of the kinase domain

AL domain

kinase domain

on Activation ALL t(9;22) (q34;q11) Clark , 1988;

The PI3K/PKB signaling module is an important mediator of cytokine signals. In hematological malignancies, mutations in cytokine receptors have been described to affect

ALL Gutierrez , 2009;

**SHIP1** SHIP1 Deactivation AML Phosphatase domain Luo , 2003 **PKB** E17K Activation T-ALL Pleckstrin homology domain Carpten , 2007;

**PP2A** Deletion Deletion/Loss AML Cristobal , 2011

ALL

K663Q Activation AML First mutation outside JM and

mutation Activation AML Extracellular (EC) domain of

mutation Activation AML Activation loop (AL) of the

**3.1.3 Activating mutations upstream of PI3K/PKB signaling pathway** 

**in: Location References** 

ALL Helical domain p110<sup>α</sup> Lee , 2005; Horn ,

line Exons 2 through 5 Sakai , 1998

line Exons 2 through 5 Aggerholm , 2000

heterozygous Gutierrez , 2009

the kinase Yuzawa, 2007

2008

Gutierrez , 2009

Parcells , 2006

Reviewed by Scholl , 2008

Dicker , 2010

Varticovski , 1991

**Detected** 

date, no other mutations in PKB have been described.

**loss** 

**PTEN** PTEN Deletion T-ALL Homozygous and

Deletion ALL cell

Deletion AMl cell

Less

mutation Activation AML &

 **Mutation Activation/** 

**PI3K** E545A Activation AML &

**Flt3** Flt3-ITD Activation AML &

**Ras** Mutations Activation AML &
