Emily Powley¹, Steven Lane², Cyriac Abraham^1
1Mater Pathology, ²Royal Brisbane and Women's Hospital, Cancer care services

Acute Myeloid Leukaemia (AML) occurring in patients treated for Chronic Lymphocytic Leukaemia (CLL) is widely reported and usually attributed to prior cytotoxic therapy. AML developing in the setting of treatment naïve CLL is extremely rare with conflicting evidence for a single cell of origin and an unknown optimal treatment.^1-5 

A 76 year old female presented with 1 week of fatigue and bruising. The patient had an incidental diagnosis of CLL-type high count monoclonal B lymphocytosis (MBL) seven years earlier which subsequently progressed to CLL, that was asymptomatic and not requiring treatment. Automated full blood count (FBC) results demonstrated an increase in White Cell Count (WCC) to 175x10⁹/L on admission, from 19.6x10⁹/L 9 months earlier. Blood film examination demonstrated 40% blast cells and 50% small mature lymphocytes with smudge cells present.

A diagnosis of NPM1 mutated AML (WHO2022) was made following bone marrow biopsy and further molecular testing. Core myeloid gene panel of 37 genes identified a Type A NPM1 mutation at a variant allele frequency (VAF) of 23.89%, FLT3 ITD mutation at a VAF of 43.08% and two DNMT3A-non R882 variants at VAFs of 33.22% and 33.32%. 

This case raises a number of interesting discussion points. Whether these malignancies arise from a single common progenitor cell population is unclear from routine molecular analysis. The mutational profile in the setting of AML developing in a patient with treatment naïve CLL is not well described. The potential implications for therapeutic approaches are also unclear.

 
References

1.     Ornellas De Souza MH, de Souza Fernandez T, Diamond HR et al. Cytogenetic and immunophenotypic evidence of independent clonal origins of concomitant chronic lymphocytic leukaemia and acute myeloid leukaemia. Eur J Haematol 2001; 66: 281-283.

2.     Gottardi M, Gattei V, Degan M et al. Concomitant chronic lymphocytic leukemia and acute myeloid leukemia: evidence of simultaneous expansion of two independent clones. Leuk Lymphoma 2006; 47: 885-889.

3.     Lu CM, Murata-Collins JL, Wang E, et al. Concurrent acute myeloid leukemia with            

inv(16)(p13.1q22) and chronic lymphocytic leukemia: molecular evidence of two separate diseases. Am J Hematol 2006; 81: 963-968.

4.     Zhang R, Kim YM, Lu X et al. Characterization of a novel t(2;5;11) in a patient with concurrent AML and CLL: a case report and literature review. Cancer Genet 2011; 204: 328-333.

5.     Chen RR, Zhu LX, Wang LL et al. Synchronous diagnosis and treatment of acute myeloid leukaemia and chronic lymphocytic leukaemia: Two case reports. World J Clin Cases 2021; 9(30): 9114-9150.