Tackling Secondary Myelodysplasia in Renal Disease: The Role Molecular Testing in Myelodysplastic Neoplasm
Authors: Elmagarmid Khadija , Attyani Leena , Soliman Dina Sameh , Fernyhough Liam , Gameil Amna 
Published: December 2024

Introduction
Myelodysplastic neoplasm (MDS) is a clonal hematopoietic stem cell disorder characterized by dysplasia and ineffective hematopoiesis. Prolonged renal disease can lead to direct bone marrow (BM) suppression through uremic toxin, promoting pro-oxidative stress and creating a pro-inflammatory environment that can alter BM hematopoiesis and suppress erythropoiesis. Medications used in the treatment of renal disease as well as the accumulation of toxins lead to deficiencies in specific trace elements, all of which may be considered disruptive to the BM environment and promote pancytopenia. Koolen De Vries, or 17q21.31 microdeletion syndrome, is a rare genetic disorder characterized by intellectual disability and developmental delay. However, this syndrome does not directly impact hematopoiesis.
Method and Results
We report a 33-year-old woman known to have Koolen-De Vries syndrome and steroid-resistant nephrotic syndrome for 3 years before her presentation. She presented with weight loss, nausea, and vomiting for 1 month. Her full blood count showed pancytopenia (WBC 1.4*10^9/L, ANC 1.3 *10^9/L, Hb 7.7 g/dL, and platelets 60 *10^9/L. Her blood chemistry showed very high creatinine 265 µmol/L (62-106 µmol/L) and high LDH 342 U/L. Urine culture grew ESBL Klebsiella pneumoniae that responded to antibiotics. Despite improvement in inflammatory parameters, she remained severely pan cytopenic requiring transfusion support so a BM examination was performed. BM aspirate was hypercellular with significant dysmegakaryopoiesis, significant dyserythropoiesis, and dysgranulopoiesis. Iron stain showed 48% ring sideroblasts (RS). There was no increase in blasts (1%). The karyotype was normal. A presumptive diagnosis of MDS with RS and multilineage dysplasia (MDS-RS-MLD) was made while awaiting molecular testing. However, other secondary causes of myelodysplasia including lead poisoning and copper deficiency were considered. Molecular genetics by next-generation sequencing (NGS) using a myeloid panel including SF3B1 was negative and the diagnosis of MDS was questioned in the absence of a supporting clonal marker. The patient progressed to anuric ESRD and was started on regular hemodialysis. Serum copper level was measured and found to be deficient 8.1umol/L (11.8-22.8) despite being collected after Hemodialysis. The patient responded to erythroid stimulating agents with an improvement in Hb and became transfusion-independent while continuing regular hemodialysis.
After the improvement in hematological parameters, she was considered for a renal transplant. Her BM was repeated almost 2 years later, showing no significant dysplasia, and no increase in blasts or ring sideroblasts. Repeated NGS (myeloid panel) did not show any clinically significant variants that would suggest myeloid neoplasia. The findings from this case resulted in the exclusion of a hematologic disease.
Conclusions
Our patient was initially misdiagnosed as MDS based on the prominent multilineage dysplasia. Copper deficiency-induced sideroblastic anemia (probably caused by high zinc) should be considered in cases with pancytopenia in the setting of long-standing renal impairment. This would necessitate screening for trace element deficiencies.Non-neoplastic causes of MDS with RS include copper deficiency which would necessitate assessment of trace elements, especially in patients with renal disease. The establishment of clonality by molecular genomics is crucial for the establishment of clonality and distinguishing MDS from its benign mimickers.