1. EAHP Bone Marrow Workshop
Familial GATA-2 mutation resulting in MonoMAC syndrome
Frances Rosario Quinones, MD
Memorial Sloan Kettering
Cancer Center

2. Clinical History
50 F with history of borderline neutropenia (ANC )
Skin rashes
Perianal warts
Waxing and waning panniculitis
Family history
Mother of two teenage boys with monosomy 7 MDS S/P unrelated HSCT at our institution
One child with uveal melanoma and papillary thyroid cancer
Past medical history
Mycobacterium kansasii infection in lymph node (04/2011)
Work up revealed pancytopenia and the patient underwent a bone marrow biopsy

3. Clinical History Bone marrow (2011)
Refractory cytopenia with multilineage dysplasia and no increase in blasts
Cytogenetics: 46 XX [20]
Bone marrow (2013)
No morphologic features of dysplasia
The patient presents to our institution for follow up in July 2015

4. Mildly hypocellular marrow
Low Power View
Mildly hypocellular marrow

5. Few hypolobated megakaryocytes (green arrow)
Medium Power View
Few hypolobated megakaryocytes (green arrow)

6. Occasional bi-nucleated erythroids
Bone Marrow Aspirate
Occasional bi-nucleated erythroids

7. Flow Cytometry, Monocyte Gate
Normal Control
Monocytes (pink) comprised 0.07% of the patient’s white blood cells.
Patient, marked monocytopenia

8. Flow Cytometry, Myelomonocytic Tube
Normal granulocyte maturation (green), mild increase in eosinophils (yellow), and near absence of monocytes (pink)
Near absence of monocytes and CD123-positive plasmacytoid dendritic cells (red arrow)

9. Flow Cytometry, Blast Tube
Mild expansion of CD34-positive blasts, with reduced expression of CD33 and abnormal expression of CD7.

10. Comprehensive Genomic Profiling
DNA sequencing identified a GATA2 G199fs*22 mutation in the patient as well as her two sons.
ASXL1 (G646fs*12) mutation in patient’s bone marrow

11. Final Diagnosis
Bone marrow, right posterior iliac crest, trephine biopsy and aspirate smears:
Hypocellular marrow with maturing trilineage hematopoiesis, minimal dysplastic changes, and no increase in blasts.
Flow cytometry
Near absence of monocytes (0.07% of WBC) and plasmacytoid dendritic cells, as well as a mild expansion of CD34-positive blasts, with reduced expression of CD13 and CD117 and abnormal expression of CD7.
Molecular Studies
GATA2 G199fs*22 mutation in patient and sons

12. Interesting Features
Evolution of a myeloid neoplasm in a patient with GATA-2 mutation which resulted in MonoMAC syndrome
ASXL1 mutations as “trigger” for the development of overt MDS
The onset of MonoMAC syndrome may precede full blown MDS by years
Increased awareness of the role of GATA2 in hematopoiesis can lead to earlier detection of MonoMAC syndrome and proper risk stratification.

13. References
Spinner MA, Sanchez LA, Hsu AP, Shaw PA, et al. GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood Feb 6;123(6):
Hsu AP, Sampaio EP, Khan J, Calvo KR, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood Sep 8;118(10):
Vinh DC, Patel SY, Uzel G, Anderson VL, Freeman AF, et al. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood Feb 25;115(8):
Bödör C, Renneville A, Smith M, Charazac A, Igbal S, et al. Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival. Haematologica June :