Myeloid molecular profile identifies mutations

[JoMac53]

So I had an initial consult at RWJ with the transplant team doctor.

He apparantly went on to do additional testing on the slides from my most recent bone marrow biopsy from about a month before because I had not had any mutations reported before and my regular onco doc wasn't aware of these results until I showed him the report myself.

Here is the report:

Pathology Consult Report
Microscopic Description Bone marrow aspirate differential count is performed on the touch prep slide.

Neutrophils/precursors 39%,
lymphocytes 8%,
monocytes 21%,
blasts 5%,
plasma cells 2%,
eosinophils 2%,
erythroids 22%.

Erythropoiesis shows dysplasia.
Granulopoiesis is predominantly left sifted.
Monocytic lineage is expanded and appears mature.
Seven percent myeloblasts are noted.
On core biopsy stainable iron stores are present.
No reticulin fibrosis is seen.
Cytogenetic analysis shows a normal female karyotype.
Flow cytometry analysis identifies 5% myeloblasts with expanded monocytic gate (26%).

Myeloid molecular profile identifies mutations in
ASXL1,
EZH2 (DOUBLE),
PTPN11,
RUNX1,
STAG2
TET2 GENES.
The presence of these mutations is suggestive of an abnormal neoplastic clone.

NOTE: Correlate with peripheral monocytic counts to evaluate for chronic myelomonocytic leukemia.

Final Pathologic Diagnosis: MYELODYSPLASTIC SYNDROME WITH EXCESS BLASTS 1.

COMMENTS: Hypercellular marrow (80% cellularity) with multilineage dysplasia and dysplastic megakaryocytes. Approximately 5% myeloblasts are detected on CD34 stains. Flow cytometry study identifies approximately 5% myeloblasts and increased numbers of monocytic lineage cells. These cells co-express CD14 and CD64 and are CD56 negative and show no aberrant loss of myeloid antigens. Cytogenetic analysis shows a normal female karyotype. Clot section shows hypercellular marrow particles with left shift and scattered dysplastic megakaryocytes.

So the diagnosis hasn't changed but I have to dig out my first bmb report from a year ago to compare the results. I think the cellularity has increased and there was nothing about mutations, antigens, chronic myelomonocytic leukemia, monocytic gate, and I have to ask the doc about stainable iron stores, from the same biopsy the original report says there aren't any but the consult reports says there are, so I'm not clear on that.

Anyone know anything off the top of their heads about these mutations or anything else in the report? I'm off to research it all but sometimes it's easier if someone here already knows what's what.

Thanks.
Joanne

[JoMac53]

Well, from what I found online it doesn't look good.

ASXL1 = generally associated with signs of aggressiveness and poor clinical outcome, prognostic biomarker, associated with shorter overall survival

EZH2 = prognostic biomarker, associated with shorter overall survival

PTPN11 = oncogene, potential to cause normal cells to become cancerous

RUNX1 = prognostic biomarker, associated with shorter overall survival

STAG2 = has been associated with less favorable clinical outcomes

TET2 = neutral or favorable prognostic biomarker however shorter overall survival following hematopoietic stem cell transplantation.

[Neil Cuadra]

Joanne,

These negative outcomes would presumably make you a high risk case without treatment. During a transplant, you'd expect those faulty cells to be replaced. Have they indicated if any of these bone marrow biopsy results are of prognostic value for a transplant?

[JoMac53]

This report just showed up in my online health records. I didn't even know they were going to do further testing on the bone marrow slides. I have a followup appointment in two weeks and I'll definitely ask about it.

[Rarity]

My husband has 3 of those faulty cells. He is post transplant now so there should be none now. He did not go to transplant until almost a year later. This was determined with his last bmb which showed disease progression which took him to transplant. Now I'm concerned about the TET2 after reading your post.

[JoMac53]

Rarity, after further research I've come to the conclusion that it's almost impossible to make any sense of this on my own. On PubMed I found articles that directly contradict each other on the effect of having a TET2 mutation. Also, what kind of mutation - insertion, deletion? - and on one copy or both has an effect. And it depends on which other mutations one has and the order in which the mutations were acquired. So it's very complex and each person is really unique. I wouldn't add it to my list of worries post transplant and I'm not going to let myself worry about it pre-transplant, either.

[Rarity]

You are right about contradiction and uniqueness with MDS JoMac. I thought maybe I misunderstood and that was concrete. Phew! Dr.s should explain more about this if they don't already. Take care and keep up the fight!