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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 2009Adopted in 2016 update of WHO as provisional entitylacks 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 MRDM>F15% 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 subgroups1)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?
WHAT ARE THERAPIES IN TRIALS?Anecdotal reports show responses of ABL class Ph-like ALL to TKI'sMDACC trial tested low-dose ruxolitinib with hyper-CVAD in r/r CRLF2-R/JAK-mutant AL
well tolerated, but
efficacy.Currently TKI's/JAK inhibitorsnot FDA approved for this.
Diagnostic recommendations:NCI HR pedi B-ALL&adult B-ALL- flow cytometry including anti-CRLF2 antibody
routine cytogeneticsFISH for ABL1, ABL2, CRLF2, EPOR, JAK2, and PDGFRBThough 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 respectivelyStepwise 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
