🚩mini #tweetorial on Ph like ALL
1⃣/8⃣
⚡️“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
1⃣/8⃣
⚡️“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
2⃣
⚡️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.
⚡️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.
3⃣
💡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
💡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
4⃣WHAT 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
➗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
5⃣WHAT ARE TARGETS FOR THERAPY?
⚡️This image from @ArchivesPath sums it all beautifully.
⚡️This image from @ArchivesPath sums it all beautifully.
6⃣WHAT 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 AL⏩well tolerated, but⏬efficacy.
‼️Currently TKI's/JAK inhibitors⏩not FDA approved for this.
⚡️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 AL⏩well tolerated, but⏬efficacy.
‼️Currently TKI's/JAK inhibitors⏩not FDA approved for this.
7⃣Diagnostic recommendations:
⚡️NCI HR pedi B-ALL&adult B-ALL- flow cytometry including anti-CRLF2 antibody➕routine cytogenetics➕FISH for ABL1, ABL2, CRLF2, EPOR, JAK2, and PDGFRB
🚩Though these are beinmg currently recommended, it remains a goal unacheievable in LIC like ours
⚡️NCI HR pedi B-ALL&adult B-ALL- flow cytometry including anti-CRLF2 antibody➕routine cytogenetics➕FISH for ABL1, ABL2, CRLF2, EPOR, JAK2, and PDGFRB
🚩Though these are beinmg currently recommended, it remains a goal unacheievable in LIC like ours
8⃣FUTURE:
⚡️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
⚡️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
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