Discover and read the best of Twitter Threads about #mpnsm
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The wonderful thing about @ASH_hematology Annual Meetings is the fruitful mix of clinic and basic research presentations.
Let's finish off our myelofibrosis coverage about new insights into biology and potential therapeutic targets.
🧵with #ASH22 abstracts
#MedTwitter #mpnsm
Let's finish off our myelofibrosis coverage about new insights into biology and potential therapeutic targets.
🧵with #ASH22 abstracts
#MedTwitter #mpnsm
Short background:
-driver mutations JAK2, CALR or MPL in 90%
-in concert with epigenetics (eg ASXL1, DNMT3A, SRSF2...)
-aberrant megakaryocytes as quintessence->reduced GATA1 protein expression and plethora of pro-inflammatory cytokines & extra-cellular matrix components 1/15
-driver mutations JAK2, CALR or MPL in 90%
-in concert with epigenetics (eg ASXL1, DNMT3A, SRSF2...)
-aberrant megakaryocytes as quintessence->reduced GATA1 protein expression and plethora of pro-inflammatory cytokines & extra-cellular matrix components 1/15
You read a lot about "novel" drugs in myelofibrosis.
But you need to know how to walk before you fly.
JAK inhibitors were the first to revolutionize myelofibrosis treatment.
Let's recap what they are & what we still dont know.
🧵with #ASH22 abstracts
#MedTwitter #mpnsm
But you need to know how to walk before you fly.
JAK inhibitors were the first to revolutionize myelofibrosis treatment.
Let's recap what they are & what we still dont know.
🧵with #ASH22 abstracts
#MedTwitter #mpnsm
Janus kinase:
-intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway
-name taken from the 2-faced Roman god of beginnings, endings and duality, because JAKs possess near-identical phosphate-transferring domains 2/17
-intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway
-name taken from the 2-faced Roman god of beginnings, endings and duality, because JAKs possess near-identical phosphate-transferring domains 2/17
There are currently 4 JAK inhibitors for MF:
ruxolitinib
fedratinib
pacritinib
momelotinib
Let's quickly present them, followed up by #ASH22 abstracts. 3/17
ruxolitinib
fedratinib
pacritinib
momelotinib
Let's quickly present them, followed up by #ASH22 abstracts. 3/17
Let's talk about bone marrow fibrosis in myelofibrosis.
When we hear fibrosis, we think lung (IPF) or liver (cirrhosis), devastating conditions.
The beauty about marrow fibrosis: it's reversible with allogeneic BMT.
Let's start🧵with new #ASH22 abstracts
#mpnsm #MedTwitter /19
When we hear fibrosis, we think lung (IPF) or liver (cirrhosis), devastating conditions.
The beauty about marrow fibrosis: it's reversible with allogeneic BMT.
Let's start🧵with new #ASH22 abstracts
#mpnsm #MedTwitter /19
Bone marrow fibrosis (BMF) is characterized by the increased deposition of reticulin fibers and in some cases collagen fibers. Scoring of BMF is primarily dependent on manual grading by the hematopathologist based on the density and type of fibrosis. 1/19
Besides myelofibrosis, there are several hematologic and non-hematologic disorders that are associated with increased BMF that differ in composition (either reticulin-only or reticulin plus collagen). 2/19
Part 2 of the GOLDI-lox preprint set, led by @andrewdunbar_md and @bowman_rl. Q: If you had a system which can test oncogenic dependency in context of co-mutant disease alleles, what question would you ask? For us, it was simple; JAK2V617F! #mpnsm
biorxiv.org/content/10.110…
biorxiv.org/content/10.110…
The role of JAK2V617F in MPN pathogenesis has long been demonstrated, and expression of JAK2V617F induces MPN in vivo as shown by many groups including @mullallylab, Tony Green, Radek Skoda, and Jean-Luc Villeval.
The role of JAK2V617F in MPN pathogenesis has long been demonstrated, and expression of JAK2V617F induces MPN in vivo as shown by many groups including @mullallylab, Tony Green, Radek Skoda, and Jean-Luc Villeval.
The story of 1 day in the life of a #hematopathologist… I’m too exhausted to make a fancy educational thread but here are some amazing 🔬 pics for your viewing pleasure. I diagnosed all cases in one day 🤯 only at @MDAndersonNews Happy almost weekend people 🥂 #hemepath 🧵 1/n
Myeloproliferative neoplasm w/ concurrent BCR::ABL1 and JAK2 V617F ..the megekaryocyte morphology is clue to something beyond CML #mpnsm #PathOutPic 2/
BPDCN with perfect so-called “hand mirror” (red) and “pearl necklace” (black) morphology #BPDCN #PathOutPic 3/
Do COVID-19 mRNA vaccines result in antibody production in MPN patients, particularly those on treatment? Data from 74 patients from the MSK Leukemia service (@MartinTallman ) published today:
rdcu.be/cAQ82 #mpnsm
rdcu.be/cAQ82 #mpnsm
We studied 22CML, 14ET, 14PV, 22MF and 2 MPN-BP patients, (on treatment or on observation).
71 of 74 patients became seropositive after 2 doses of Pfizer or Moderna vaccine.
71 of 74 patients became seropositive after 2 doses of Pfizer or Moderna vaccine.
2 patients on ruxolitinib and 1 patient on ponatinib did not respond to vaccine. A trend toward lower antibody levels noted in ruxolitinib treated patients was observed. A trend toward higher antibody levels noted in some interferon treated patients.
What happens to hematopoietic transplant recipients who develop #COVID19?
Transplant recipients and transplanters have been asking this question ever since the pandemic began.
Our analysis using @CIBMTR data is out today in @TheLancetHaem thelancet.com/journals/lanha…. 1/
Transplant recipients and transplanters have been asking this question ever since the pandemic began.
Our analysis using @CIBMTR data is out today in @TheLancetHaem thelancet.com/journals/lanha…. 1/
While there have been close to 100,000 papers related to COVID-19 listed on @NCBI @NLM_NIH #Pubmed, there are very few that address outcomes after #COVID19 in #BMTsm patients, a few are listed in the next tweet: 2/
1. Spanish experience from @GETH_info onlinelibrary.wiley.com/doi/10.1002/pb…
2. Chicago (@RushMedical, @UChicago & @NUFeinbergMed) & New York City (@MountSinaiNYC) experience in @LeukemiaJnl nature.com/articles/s4137…
3. @sloan_kettering experience in @jclinicalinvest jci.org/articles/view/… 3/
2. Chicago (@RushMedical, @UChicago & @NUFeinbergMed) & New York City (@MountSinaiNYC) experience in @LeukemiaJnl nature.com/articles/s4137…
3. @sloan_kettering experience in @jclinicalinvest jci.org/articles/view/… 3/
We studied newly diagnosed patients with ET and PV,
reconstructing the lineage history & differentiation trajectories of individual JAK2V617F HSC - here is our preprint will full details #MPNsm
biorxiv.org/content/10.110…
reconstructing the lineage history & differentiation trajectories of individual JAK2V617F HSC - here is our preprint will full details #MPNsm
biorxiv.org/content/10.110…
Our work will be presented by Debra Van Egeren, a grad student @Harvard in an oral abstract @ASH_Hematology #ASH20. This is a team effort across @DanaFarber @BrighamHeme @MGHCancerCenter @df_hcc @BCHStemCell @embl ash.confex.com/ash/2020/webpr…
3. We performed combined single-cell genotyping & transcriptomic profiling on CD34+ enriched BM from newly diagnosed patients with ET and PV, plus whole genome sequencing for lineage tracing of JAK2-mutant HSC.
1/ "How long have I had it for?"
Our patients with #bloodcancer have always wanted to know. We set out to answer it. We studied patients with MPN #mpnsm and found quite unexpected results. Excited to share our preprint biorxiv.org/content/10.110…
Our patients with #bloodcancer have always wanted to know. We set out to answer it. We studied patients with MPN #mpnsm and found quite unexpected results. Excited to share our preprint biorxiv.org/content/10.110…
2/ We took single blood cells from patients with MPN and grew each cell into a colony. We then sequenced each colony's whole genome (>950 whole genomes).
3/ We used DNA mutations to trace the ancestral relationships between colonies - building a "family tree" of blood production for each patient. We could then time the cancer driving genetic events and trace how the mutant clones expanded over the patient’s life.
Hi #MedTwitter, let's talk about the workup of polycythemia and making a diagnosis of polycythemia vera (PV) vs. secondary polycythemia! #mpnsm #tweetorial @MedTweetorials
Based on the WHO guidelines, the following values constitute polycythemia:
In men: Hgb >16.5g/dL or Hct > 49%
In women: Hgb > 16 or Hct > 48%
Polycythemia should be confirmed by a subsequent CBC. Below is an image of the ddx of polycythemia (Keohane et al 2013)
In men: Hgb >16.5g/dL or Hct > 49%
In women: Hgb > 16 or Hct > 48%
Polycythemia should be confirmed by a subsequent CBC. Below is an image of the ddx of polycythemia (Keohane et al 2013)
Our patient's polycythemia has been confirmed! What to do next? Make sure to ask questions related to hyperviscosity (eg chest pain, dyspnea, headache, vision changes, confusion), thrombosis/bleeding hx, and PV-related symptoms (pruritus after baths, erythromelalgia, B-symptoms)
