mini #tweetorial on Ph like ALL
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“Ph-like”or BCR-ABL1-like ALL was described by the COG& Dutch COG by GEP in 2009
Adopted in 2016 update of WHO as provisional entity
lacks the BCR-ABL1 translocation but similar gene expression as Ph+B ALL
#medtwitter #hemonc #leusm

Ph-like ALL dont have BCR-ABL1,ETV6-RUNX1,TCF3-PBX1,MLL rearrangements or high hyper-diploidy.
Mutated IKZF1 is a hallmark of Ph-like ALL like Ph+ ALL.
CHARACTERISTICS:
TLC>100 000/uL at diagnosis
end of induction MRD
M>F
15% of childhood&25% in AYAs.

WHY ALL THIS INTEREST IN THIS SUBTYPE?
OS of pediatric ALL is 80%,with some having>98% cure rate
Like Ph+ALL, it has high rate of treatment failure& poor OS
BUT with a number potential for targeted therapy due to genetic alterations activating tyrosine kinase signaling

WHAT ARE THE GENETIC ALTERATIONS?
6 subgroups
1)rearrangements of CRLF2: >50%

2)ABL rearrangements- Amenable to therapy with TKI's

3)JAK2+/- EPOR rearrangements- amenable to therapy with JAK inhibitors
4) other mutation in JAK/STAT
5) other kinase mutations
6)RASmutations

WHAT ARE TARGETS FOR THERAPY?
This image from @ArchivesPath sums it all beautifully.

WHAT ARE THERAPIES IN TRIALS?
Anecdotal reports show responses of ABL class Ph-like ALL to TKI's
MDACC trial tested low-dose ruxolitinib with hyper-CVAD in r/r CRLF2-R/JAK-mutant ALwell tolerated, butefficacy.
Currently TKI's/JAK inhibitorsnot FDA approved for this.

Diagnostic recommendations:
NCI HR pedi B-ALL&adult B-ALL- flow cytometry including anti-CRLF2 antibodyroutine cytogeneticsFISH for ABL1, ABL2, CRLF2, EPOR, JAK2, and PDGFRB
Though these are beinmg currently recommended, it remains a goal unacheievable in LIC like ours

FUTURE:
several clinical trials of dasatinib&ruxolitinib with chemotherapy are in progress
HSP90 inhibitors&retinoids represent potential therapeutic agents in JAK&IKZF1 mutant cases respectively
Stepwise algorithms as shared above might help in identifying this subtype

Kindly add on, correct and share ur experiences in diagnosing and managing Ph like B-ALL, respected teachers @DrGPrakash @bagalbp @satya_yadav @rahulbhargavadr @BollamRajesh4 @RanjitKSMD @drkunalsehgal @veeronco @DrESHAJ9 @DrGauravNarula @THilalMD @IJMPOofficial @ReetuJain19