*4.1.2 IKZF1 deletions*

The *IKZF1* deletion has recently emerged as a novel genomic marker in childhood ALL. This subtype is commonly seen in older children, those with higher WBC counts, Down syndrome (DS), BCR-ABL and Ph-like ALL [55, 59, 62, 63]. Increased association is also seen with *CRLF2* mutations [62]. *IKZF1* deletion is an independent poor prognostic genomic feature in multivariate analysis [64–68]. The AIEOP-BFM group showed *IKZF1* deletions confer a poor prognosis only in the high end-induction MRD group with co-existent *CDKN2A*, *CDKN2B*, *PAX5*, or *PAR1* mutations [69].

### *4.1.3 JAK-pathway mutations.*

*JAK* mutations are commonly found in Ph-like ALL (20%) and are also associated with *CRLF2* mutations [33]. These are also seen in approximately 15% of children with DS ALL [34, 70, 71]. Identification of this mutation is essential as it has therapeutic implications with responses seen both *in vitro and in vivo* to TKIs [72]. The ongoing phase II trial AALL1521 is testing upfront addition of ruxolitinib to chemotherapy for *CRFL2* rearranged or *JAK*-pathway mutant children with ALL [73].
