Jump to comment:

• Chronic neutrophilic leukaemia: a molecularly defined disease?
  Stephen E. Langabeer
  Published on: 18 April 2016

• Published on: 18 April 2016

  Chronic neutrophilic leukaemia: a molecularly defined disease?

  • Stephen E. Langabeer, Clinical Scientist

  In their recent review, Uppal and Gong provided a comprehensive overview of the pathological findings in the uncommon myeloproliferative neoplasm of chronic neutrophilic leukaemia (CNL) [1]. Subsequent to the landmark discovery of somatic mutations in the CSF3R gene in CNL patients which provided a rationale for adoption of tyrosine kinase inhibitor therapies, studies on further cohorts now suggest that activating CSF3R...

  Show More

  In their recent review, Uppal and Gong provided a comprehensive overview of the pathological findings in the uncommon myeloproliferative neoplasm of chronic neutrophilic leukaemia (CNL) [1]. Subsequent to the landmark discovery of somatic mutations in the CSF3R gene in CNL patients which provided a rationale for adoption of tyrosine kinase inhibitor therapies, studies on further cohorts now suggest that activating CSF3R mutations are found solely in World Health Organization-defined CNL without a co-existing monoclonal gammopathy amongst other myeloproliferative neoplasms [2, 3]. Identification of CSF3R mutations would now make the diagnosis of CNL no longer one of exclusion. As discussed by Uppal and Gong, secondary mutations in other genes such as SETBP1, ASXL1 and CALR have been observed in conjunction with those in CSF3R.

  How therefore are those rare CNL cases harbouring the JAK2 V617F mutation [4, 5] now to be classified given this proposal? Throughout the literature are several reports of polycythaemia vera and to a lesser extent, primary myelofibrosis, progressing to a proliferative neutrophilic phase (as opposed to myelofibrotic or leukaemic transformation) that mimics the morphological features of CNL. In one such recently reported case in which some of the characteristic morphological features of the underlying JAK2 V617F-positive polycythaemia vera persisted, no CNL- associated CSF3R mutations were found [6]. Does the possibility therefore exist that those historical CNL JAK2 V617F-positive cases represent patients with polycythaemia vera or primary myelofibrosis presenting in this terminating neutrophilic stage? Anecdotal evidence supporting this speculation comes from the favourable clinical response of a JAK2 V617F- positive CNL patient treated with interferon-?; an agent with proven efficacy in other myeloproliferative neoplasms [7]. Consequently it might therefore be argued that CNL is a distinct molecular entity and similar to World Health Organization-defined atypical chronic myeloid leukaemia, is a JAK2 V617F-negative disease [8].

  It is acknowledged that there exists a spectrum of clinical, morphological and molecular features even in such a rare disease as CNL and it is hoped that the next revision of World Health Organization classification of haematopoietic malignancies provides both clarification and consensus.

  REFERENCES

  1. Uppal G, Gong J. Chronic neutrophilic leukaemia. J Clin Path 2015;68:680-4.

  2. Pardanani A, Lasho TL, Laborde RR, et al. CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia 2013;27:1870-3.

  3. Li B, Gale RP, Xiao Z. Molecular genetics of chronic neutrophilic leukemia, chronic myelomonocytic leuekmia and atypical chronic myeloid leukemia. J Hematol Oncol 2014;7:93.

  4. McLornan D, Percy MJ, Jones AV, Cross NC, McMullin MF. Chronic neutrophilic leukemia with an associated V617F JAK2 tyrosine kinse mutation. Haematologica 2005;90:1696-7.

  5. Lea NC, Lim Z, Westwood NB, et al. Presence of the JAK2 V617F tyrosine kinase mutation as a myeloid-lineage specific mutation in chronic neutrophilic leukemia. Leukemia 2006;20:1324-6.

  6. Castelli R, Cugno M, Gianelli U, et al. Neutrophilic progression in a case of polycythemia vera mimicking chronic neutrophilic leukemia: clinical and molecular characterization. Pathol Res Pract 2015;211:341-3.

  7.Zhang X, Pan J, Guo J. Presence of the JAK2 V617F mutation in a patient with chronic neutrophilic leukemia and effective response to interferon ?-2b. Acta Haematol 2013;130:44-6.

  8. Fend F, Horn T, Koch I, Vela T, Orazi A. Atypical chronic myeloid leukemia as defined in the WHO classification is a JAK2 V617F negative neoplasm. Leuk Res 2008;32:1931-5.

  Conflict of Interest:

  None declared

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top