Chronic Myeloid Neoplasms
Chronic myelomonocytic leukemia (CMML)

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 8 March 2017, last major update August 2011

Copyright: (c) 2002-2017,, Inc.

PubMed Search: Chronic myelomonocytic leukemia [title] (CMML)

Cite this page: Chronic myelomonocytic leukemia (CMML). website. Accessed June 22nd, 2018.
Definition / general

Variable clinical and hematologic presentations:
  1. Myelodysplastic features of blood cytopenias, ineffective hematopoiesis, dysplastic changes and increased blasts resembling refractory anemia, refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts; plus monocytosis (monocytes may have dysplastic features)
  2. Marked leukocytosis with monocytosis, organomegaly, normal hematopoiesis, normal red blood cell and platelet counts, no / minimal dysplastic changes or excess blasts; previously called Philadelphia chromosome negative CML

  • 80% of cases arise de novo; 20% arise from prior myelodysplasia, occasionally with monocytosis (Am J Clin Pathol 2006;126:789)
  • Splenomegaly in 30 - 50% with rare rupture (Am J Hematol 2007;82:405, Am J Surg Pathol 1983;7:197), hepatomegaly in 20%
  • May have tumor forming accumulations of CD123+ plasmacytoid monocytes in lymph nodes, bone marrow or skin (Am J Surg Pathol 2004;28:585)
  • More closely related to myelodysplasia than myeloproliferative neoplasms using loss of heterozygosity evaluation (Mod Pathol 2007;20:1166)
  • Type 1: < 5% blasts in blood or < 10% blasts in bone marrow
  • Type 2: 5 - 19% blasts in blood, 10 - 19% blasts in bone marrow or Auer rods present; also < 20% blasts in blood or marrow; poorer prognosis
  • If blasts + promonocytes are 20% of more of bone marrow differential count, classify as AML
  • Persistent peripheral blood monocytosis of more than 109/L, with monocytes > 10% of WBCs
  • No BCR-ABL1 gene fusion
  • No rearragement of PDGFRA or PDGFRB
  • < 20% blasts (includes myeloblasts, monoblasts and promonocytes)
  • Peripheral blood may have dysplastic changes typical of myelodysplasia in one or more myeloid lineages, or dysplasia may be limited to monocytes
  • Usually no marrow monocytosis (Mod Pathol 2006;19:1536)
  • In absence of myelodysplasi, diagnosis can be established if the process is clonal, if monocytosis is > 3 months and other causes for monocytosis are excluded
Case reports
  • Decitabine
  • Median survival 19 months (Cancer 2007;109:713)
  • Predictors of course of disesase include percentage of peripheral / marrow blasts, degree of leukocytosis, extent of anemia and splenomegaly / organomegaly
Microscopic (histologic) description
  • Peripheral blood: cytopenia(s), monocytes may be normal appearing or have dysplastic features of increased basophilic cytoplasm, abnormal granulation, hyperlobulated nuclei; other lineage cells may have dysplastic changes – the most common being granulocytes
  • Bone marrow: hypercellular marrow with mildly increased monocytes (but not diagnostic by itself) and increased granulocytes; may have increased reticulin fibers; variable dysplastic changes in erythroid cells and megakaryocytes; cases with eosinophilia need screening for PDGFRA, PDGFRB and FGFR1 gene abnormalities in addition to looking for causes of eosinophilia
Microscopic (histologic) images

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Images hosted on PathOut server:

Peripheral blood:

Three mature monocytes

Blast with Auer rod

Increase in mature monocytes and neutrophils

Bone marrow biopsy:

Markedly hypercellular marrow

Bone marrow smear:

Increased monocytes and monocyte precursors

Increase in monocyte
precursors and erythroid
cytoplasmic vacuoles

Promonocytes and
monocytes, neutrophils
and erythroid precursors


Alpha naphthyl acetate
and methyl green
stains (non specific esterase)

Images hosted on other servers:

Other sites:

Kidney suburothelial tissue; various images

Nature images:

Bone marrow biopsy:

Plasmacytoid monocyte nodules: H&E and CD123

Comparison with CML and atypical CML

Other sites:

Colonic infiltration


H&E and alpha naphthyl butyrate esterase

Plasmacytoid monocyte nodules: H&E and CD123

Positive stains
Flow cytometry description
  • Monocytosis with two or more aberrant phenotypes such as decreased CD14, CD13, HLA-DR, CD64 or CD36, overexpression of CD56
  • Or abnormal antigen expression of 2+ antigens plus 20% of marrow monocytes showing CD14+ expression, which is specific for CMML versus reactive monocytosis (Am J Clin Pathol 2005;124:799)
Electron microscopy images

Images hosted on PathOut server:

Monocytes are atypical with large granules

Molecular / cytogenetics description
Molecular description:
Cytogenetics description:
  • Abnormalities in 20 - 40%, including trisomy 8, monosomy 7, 7q-, abnormalities of 12p
  • Occasionally t(5;12)(q33;p13)
Differential diagnosis
  • CML (BCR-ABL1 gene fusion) and atypical CML (few monocytes identified by nonspecific esterase, no peripheral monocytosis, no CD123+ plasmacytoid monocytic nodules)