Juvenile Myelomonocytic Leukemia

Biology and Pathogenesis

Malignant monocyte-macrophage proliferation forms the basis for JMML. The biology of JMML cells is characterized by :-

• Monocyte-specific immunophenotype
  
  
• Autocrine production of tumor necrosis factor (Alpha-TNF) by the malignant monocyte-macrophage cells of JMML
  
  
• Selective hypersensitivity of JMML progenitor cells (CFU-GM) to GM-CSF.
  
  

The following pathologic events result in the growth of JMML cells:

• Bi-directional action of TNF:
  
  
  • TNF inhibits normal hematopoiesis
    
    
  • TNF induces the proliferation of the malignant monocyte-macrophage elements of JMML.
    
    
• Proliferating monocyte-macrophage elements of JMML secrete GM-CSF
  
  
• GM-CSF increases further the proliferation of the hypersensitive population of JMML cells and enhances further the release of TNF.
  
  
• Proliferating monocyte-macrophage cells also generate IL-1.
  
  

The inhibitory effect of TNF on normal hematopoiesis outweighs the normal stimulatory function of GM-CSF and IL1 and eventually results in bone marrow suppression, anemia, and thrombocytopenia

Clinical features of Juvenile Myelomonocytic Leukemia

JMML is sub classified into :-

• Juvenile chronic myelogenous leukemia (JCML) when there is :-
  
  
  • JMML morpholo1gy in the absence of t(9;22) translocation
    
    
  • Raised HbF (> 10%)
    
    
  • No monosomy 7
    
    
• Infantile monosomy 7 syndrome when there is :-
  
  
  • Presenting age less than 4 years with any type of myelodysplasia
    
    
  • Monosomy 7
    
    

Frequency
The incidence of JMML is 0.6 cases per year per million children. JMML accounts for 18% of all cases of myelodysplastic syndrome in children less than 15 years of age.

Genetics
Seven percent of JMML cases have been associated with neurofibromatosis, type 1. JMML has been described in identical twins.

Age of onset
Forty percent of cases occur before 1 year of age and 60% of cases occur before 2 years of age.

Sex
The male / female ratio is 2.1 : 1%