Typically ''atypical'': A case series of atypical chronic myeloid leukemia

ABSTRACT

Aims & Objectives: Atypical Chronic myeloid leukemia (aCML) is a rare subtype of MDS/MPN. The diagnosis of aCML has evolved over years with more evidence from cytogenetic and molecular studies. We report here a case series of three patients with aCML that was picked up based on morphology and molecular workup. Patients/Materials & Methods: Case 1 A 68-year male with incidental detection of leukocytosis on routine hemogram without organomegaly with Hb11.6 g/dL,TLC 35X103/μl,platelets 41X103/ ll,DLC My30MM5N53L8E3Baso1%. Bone marrow was hypercellular with ME ratio7.71, severe dysgranulopoiesis, 07% blasts,and dysmegakaryopoiesis (>50%). His extended MPN reflex panel (BCR-ABL1, JAK2, CALR, MPL) was negative. Provisional diagnosis of aCML was made. NGS panel revealed multiple mutations in ZRSR2, ASXL1, RUNX1, SF3B1, EZH2, TET2 genes. He has completed 6 cycles of Azacytidine and remains stable for 8 months since the diagnosis. Case 2 A 76-year old male with suspected CML presented with mild hepatosplenomegaly with Hb 8.9 g/dL,TLC 46X103/μl, platelets 75X103/μl, DLC Blast3My12MM8 N66Ly8 Mono2Baso1% and 2nRBC/100 WBCs. Bone marrow was hypercellular with ME 6.31, significant dysgranulopoiesis 03% blasts, and dysmegakaryopoiesis. His extended MPN reflex panel was negative. NGS revealed mutations in ASXL1 and KRAS genes. After diagnosing aCML he was started on hydroxyurea and remains stable after 6 months of diagnosis. Case 3 A 71-year old female with suspected CML based on moderate splenomegaly and hemogram showed Hb 8.9 g/dL,TLC 65.94X103/μl, Platelets 45X103/μl with DLC Blast1My29MM22N38Ly5Eo4Baso2% Bone marrow was hypercellular with ME 5.81, prominent left shift in granulocytic series, 01% blasts, no dysgranulopoiesis. There was significant dysmegakaryopoiesis. A provisional diagnosis of CML vs MDS/MPN was kept and was advised molecular workup. BCR-ABL1 and JAK2 mutation were negative. NGS panel revealed ASXL1 and SF3B1 gene mutations. Finally diagnosed as aCML and treated with Hydroxyurea. She developed undiagnosed fever during COVID19 lockdown and succumbed to her illness. Discussion & Conclusion: Atypical CML is a very rare entity with close differential diagnoses of accelerated phase of CML or MDS/ MPN-U. However as more awareness of this entity has emerged, more patients are subjected to NGS evaluation, thus contributing to the knowledge about this under-reported diagnosis from the third world.