Bloody Minded

Here’s a question, what do CD123, CD4 and CD56 have in common? Other than pleasing The Count on Sesame Street. Sorry, another question perhaps - what happens if you cross a plasma cell and a dendritic cell? The answers to these questions can be found on a most enigmatic myeloid cell - the plasmacytoid dendritic cell. And what happens when these rare beasts become neoplastic - why BPDCN of course. Embark on a journey into this weird and not so wonderful (but highly examinable) neoplasm with the Bloody Minded Crew 

TIMESTAMPS

 0:57 – A glimpse into Cale's psyche
 2:39 – Intro to BPDCN
 6:56 – What IS a plasmacytoid dendritic cell?
 10:24 – Pathological PDCs in BPDCN
 11:42 – Clinical presentation – lots of rash talk
 15:23 – Morphology in BPDCN
 17:48 – Immunophenotype
 21:16 – Karyotypic and molecular features
 22:44 – Treatment of BPDCN
 24:00 – A bit on prognostic markers
 25:03 – Transplant
 25:28 – Tagraxofusp
 29:15 – Other treatment options
 31:33 – Take home messages 

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“It’s pronounced nuc-ul-ophosmin” “Nucleophosmin”. “Noo-clee-o-phosmin”. FLT3-ITD got you In The Dumps? Have a Total Knowledge Deficit about TKD mutations? Struggling with the A-B-Cs of NPM1 mutations? Want to know how a cat sarcoma is somehow related to AML? Join the Bloody Minded Crew as they flit about the laboratory looking at the structure of FLT3 and NPM1, what these proteins usually do and how we test for mutations in the advanced myeloid episode.

== Edit 6/5/26 = We've been made aware that strictly speaking the current MANE approved transcript for NPM1.1 has only 11 exons and therefore the mutations are best to be considered in Exon 11 as opposed to exon 12 - in contrast to what we said. ==

Timestamps

0:52 - Bloody Minded issues a formal apology
2:40 - Introducing molecular chaperones
5:05 - What even NPM1?
9:30 - Functions of NPM1
10:55 - Molecular biology of NPM1 in disease
15:42 - Why the subtypes are important
19:53 - NPM1 prognosis
21:35 - MRD testing in NPM1
25:52 - NPM1 summary
27:13 - Intro to FLT3
28:30 - Mandatory FLT3 history
36:28 - FLT3 pathogenesis
37:37 - FLT3 structure, ITD vs TKD
41:16 - The juxtamembrane domain
42:53 - Prognostic features in FLT3
44:17 - TKD mutations
46:26 - FLT3 in the lab
50:30 - Take home messages

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U-G-L-Y, you ain't got no alibi, you dysplastic yeah yeah you dysplastic. Apologies to all the ring sideroblasts out there, but this week the Bloody Minded crew is doing a Mean Girls and judging cells by their morphology. For now we’re deciding to ignore those that would argue that it’s what’s on the inside that counts (i.e. judging by NGS… that’ll come later).

TIMESTAMPS

2:28 - For some reason, an audio podcast on visual dysplasia 
5:05 - Normal erythroid morphology 
7:17 - Dysplastic erythroid morphology 
17:32 - Normal granulocyte morphology 
20:00 - Dysplastic granulocyte morphology 
28:33 - Monocyte morphology - dysplastic at baseline 
30:33 - Normal megakaryocyte morphology 
32:24 - Dysplastic megakaryocyte morphology 
35:02 - Take Home Messages

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What do arsenic, acne tablets and Jodi Picoult have in common? Why, it must be a deep dive with Nick, Bashar and Cale on acute promyelocytic leukaemia. From buzzwords to brain bleeds, the sweetest of translocations to the cruellest of coagulopathies... The yield is almost as high as the survival rates.

TIMESTAMPS

00:57 - Bloody Minded Poetry Jam & Jodi Picoult
06:25 - APML Starts Here
08:02 - APML - Where does it fit in AML?
10:02 - Morphology & Flow
12:12 - PML::RARA - t(15;17) and rare variants
16:58 - Lab Summary
17:50 - Clinical Presentation
21:02 - APML Coagulopathy
26:46 - Treatment and Risk Stratification
33:53 - High Risk Aside
36:58 - Differentiation Syndrome

41:04 - Treatment SEs
44:18 - Microgranular Variant
47:00 - Summary and Takehomes

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After our initial intro to AML back in ep 79, we are back to dig deeper into AML this week, from pathophysiology through to treatment overview. The boys are joined by final year registrar Dr Georgina Calov who is here to cut through our nonsense and deliver some actual high yield content. And thank goodness for that, otherwise it'd be an hour of us making bad April Fool's day jokes.

Timestamps

2:09 - Introducing Dr Georgina Calov
3:34 - AML Refresher
7:12 - AML defined by recurrent genetic abnormalities
15:39 - AML defined by differentiation (aka whats with the M numbers)
18:14 - MN-pCT
19:03 - Prognostication - ELN Classification
21:58 - Diagnosing AML - Clinical
24:16 - Diagnosing AML - Lab
31:39 - New AML Workup
35:50 - Intro to Treatment - Induction in "Fit" patients
41:40 - Treatment - Consolidation & MRD
45:15 - Treatment - "Unfit"
48:02 - Treatment - Supportive
50:16 - Treatment - Relapse/Refractory
55:19 - Summary

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Cat got your tongue? Or in this case - mucositis? Does converting the acute allogeneic transplant patient who can no longer eat's medications to IV fill you with dread? In this practical for once episode join consultant haematologist Dr Alison Chandler as well as haematology pharmacists Andriana Colic & Ariana McCauley as they take us through the how to of this challenging, but very common, clinical scenario. 

Timestamps

0:58 - Nick's literal nightmare
2:18 - Today's outline
3:38 - Let's meet the A-team!
11:14 - What do you wish the haem doctors knew?
13:38 - Introducing the NBM transplant patient
15:18 - Tacrolimus
17:37 - Mycophenolate
19:51 - Ciclosporine (or cyclosporine or CsA or CyA, whatevs)
22:20 - Hot tip on TDM
23:47 - Antifungals
24:23 - Posaconazole
26:06 - Voriconazole
27:29 - Isavuconazole
28:45 - Echinocandins - mica/anidula
30:52 - Antivirals
33:27 - CMV treatment
37:41 - Antibacterials - PJP prophylaxis
39:22 - The NBM APML patient 
43:35 - Antiepileptics
46:24 - TLS prophylaxis
47:53 - Wrap up time!
50:18 - Episode summary

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Was episode 79 too light on MDS for you? “Amateurs” you said, adjusting your sellotaped glasses. If so, you’re in the right place today as we prepare to look at classification, risk stratification and treatment of myelodysplastic syndrome. You also should seek out psychiatric attention, or perhaps just go outside. But in the meantime, enjoy this episode where we’ll dig deeper into the nitty gritty of MDS! We’ve got a lot to cover so we float about between intermediate and advanced for this episode.

TIMESTAMPS

1:11 - A Very Unhinged Intro  
3:34 - Actual Content Starts Here  
5:52 - Differentials for dysplasia  
7:54 - Presentations of MDS  
12:36 - MDS Subtypes  
14:23 - MDS with del(5q)  
18:29 - Lenalidomide in del(5q)  
25:03 - MDS with SF3B1  
29:05 - MDS with biallelic TP53 inactivation  
30:26 - Bonus cytogenetic abnormalities that pop up  
31:43 - Germline mutations that predispose to MDS and AML  
37:14 - MDS with low blasts  
38:08 - Ogata Score  
39:26 - Hypoplastic MDS  
44:03 - MDS with increased blasts  
44:58 - MDS with increased blasts and fibrosis  
46:22 - Breaking News - Blasts Should Now Be Counted By Flow  
48:30 - Prognostic models for MDS  
53:36 - Treatments for MDS  
1:04:39 - Take Home Messages

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Check out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

What if the prequel had a prequel? Join Bashar, Nick and Cale as they attempt to unpack the newfangled world of clonal haematopoeisis. Find out how CHIPs can kill and no, it’s not due to eating too many of them too fast. Though that might do it too. We’ve had one spectrum, but what about a second. We need to go deeper. 

TIMESTAMPS

0:56 - A classic chippy mixup  
2:56 - Episode overview  
3:54 - Where CHIP sits in haem  
5:15 - Clonal haematopoiesis  
11:21 - What genes acquire CH?  
13:42 - CHIP  
20:09 - Clinical implications of CHIP  
24:24 - Increased mortality in CHIP  
28:54 - ICUS  
32:40 - CCUS  
35:42 - Take home messages  

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 If we’re going to truly understand myeloid disease, we must dispense with the ward and journey to the dystopian heart that beats at the centre of each dysplastic cell. Learn what is valid and in-valid as we swim across an ocean of concepts - past the basic principles of DNA and RNA, Polymerase Chain Reaction and its many many variants, Fragment Analysis and Next Generation Sequencing. Just save a little something for the swim back to clinic next week.

PS The Extra T is for TYOTT 

Timestamps

0:55 - Back in the lab, baby!
2:08 - Today's outline
6:24 - What IS molecular testing?
8:13 - The central dogma of molecular biology
14:46 - Types of genetic mutations
20:05 - Nomenclature for gene variants (advanced)
23:52 - Samples for testing
27:42 - What comes after DNA extraction
30:11 - What is PCR and how did we discover it? 
38:45 - What we do post PCR
41:27 - Quantitative and RT-PCR 
46:54 - Asking the RIGHT question
48:55 - Digital droplet PCR
50:44 - Electrophoresis
52:35 - Fragment analysis and melt curve analysis
54:33 - NGS
1:00:02 - What is a VAF?
1:05:23 - Lab governance (for haem ATs)
1:09:32 - Take home messages

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Happy marrows are all alike; every unhappy marrow is unhappy in its own way.  When haematopoiesis behaves itself, it’s frankly quite boring. When it goes rogue, it can get very creative. Join Cale, Bash and Nick as they attempt to walk through how this process goes off the rails, how MDS and AML are best understood and how dysplasia, cytopenias, blasts and clones all fit together.

TIMESTAMPS

0:55 - Our serious introduction to counterbalance last week 
1:58 - Episode overview 
2:50 - Introducing MDS 
7:12 - Risk factors for MDS 
8:53 - MDS progression 
11:13 - Complications of MDS 
13:10 - Leukaemic transformation 
15:37 - MDS epidemiology 
16:27 - Diagnosing MDS 
21:19 - What is dysplasia? 
26:44 - What we test on marrow 
35:13 - Clonality assessment in MDS 
42:29 - Caveats in diagnosing MDS 
43:18 - MDS summary (finally) 
44:09 - MDS treatment in brief 
45:37 - Intro to AML 
51:32 - Episode summary 

Support the show

Check out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au