Juvenile myelomonocytic leukemia

Classification according to ICD-10
C93.3	Juvenile myelomonocytic leukemia
ICD-10 online (WHO version 2019)

The Juvenile myelomonocytic leukemia ( JMML ) may be particularly malignant special form of leukemia are called in infants and young children with malignant transformation of hematopoietic stem cells , the monocytes precursors.

JMML is viewed as a hybrid of myelodysplastic syndromes (MDS) and myeloproliferative neoplasias (MPN).

Synonyms are: leukemia, chronic juvenile myelomonocytic , English juvenile chronic myeloid leukemia (JCML), chronic myelomonocytic leukemia of infancy and infantile monosomy 7 syndrome

distribution

The frequency is given as 1–9 in 1,000,000. The male sex is affected 2 to 3 times more often. The average age of onset is 2 years.

The JMML comprises about 30% of all childhood myelodysplastic syndromes and 2% of leukemias.

The Chronic myelomonocytic leukemia is similar to the clinical picture, but only occurs at a later age.

root cause

Depending on the underlying mutations , different forms can be distinguished:

• Acute myelomonocytic leukemia, somatic form with mutations in the MLLT11 gene at locus 1q21.3
• Juvenile myelomonocytic leukemia, somatic form with mutations in the ARHGAP26 gene at 5q31.3 or in the PTPN11 gene at 12q24.13
• Juvenile myelomonocytic leukemia with mutations in the NF1 gene at 17q11.2

Mutations in the NF1, NRAS, KRAS or PTPN11 gene are found in 75% of those affected.

Clinical manifestations

The clinical symptoms can be unspecific. The main clinical criteria are:

• paleness
• poor general condition
• Bulging of the abdomen due to massive hepatosplenomegaly
• Infiltration of the intestines and lungs

The disease is often accompanied by other changes such as impaired vision or hearing loss . Mutations in the CBL gene are often present in these combinations.

There is an association with Noonan's syndrome .

Diagnostic criteria

The diagnosis of JMML is based on the fact that a patient meets all criteria of Category 1 and at least one of Category 2 or at least two of Category 3:

• Category 1: splenomegaly ; AMC> 1000 / µL; Blast content <20%; Absence of the t (9; 22) BCR / ABL fusion gene
• Category 2: Somatic mutations in the RS or PTPN11 gene; Clinical signs of NF1 or mutations in the NF gene; Homozygous mutation in the CBL gene; Monosomy 7
• Category 3: myeloid precursors in blood serum ; WBC count > 10,000 / ul; age-related increased fetal hemoglobin ; clonal cytogenetic abnormality excluding monosomy 7 ; Hypersensitivity to GM-CSF

therapy

Treatment with a bone marrow transplant or blood stem cell donation is considered to be promising.

literature

• P. Satwani, J. Kahn, CC Dvorak: Juvenile myelomonocytic leukemia. In: Pediatric clinics of North America. Vol. 62, No. 1, February 2015, pp. 95-106, doi: 10.1016 / j.pcl.2014.09.003 , PMID 25435114 (review).
• A. Yoshimi, S. Kojima, N. Hirano: Juvenile myelomonocytic leukemia: epidemiology, etiopathogenesis, diagnosis, and management considerations. In: Pediatric drugs. Vol. 12, No. 1, 2010, pp. 11-21, doi: 10.2165 / 11316200-000000000-00000 , PMID 20034338 (review).
• H. Pechumer, C. Bender-Götze, JU Walther, T. Klingebiel, G. Ehninger, M. Suttorp, N. Schmitz: Juvenile chronic leukemia and chronic myelomonocytic leukemia. Experience with bone marrow transplantation in childhood based on 5 cases. In: Monthly Pediatric: Organ of the German Society for Pediatrics. Vol. 140, No. 5, May 1992, pp. 307-312, PMID 1614461 .

Individual evidence

1. ↑ ^{a b} ML Loh, DS Sakai, C. Flotho, M. Kang, M. Fliegauf, S. Archambeault, CG Mullighan, L. Chen, E. Bergstraesser, CE Bueso-Ramos, PD Emanuel, H. Hasle, JP Issa , MM van den Heuvel-Eibrink, F. Locatelli, J. Stary, M. Trebo, M. Wlodarski, M. Zecca, KM Shannon, CM Niemeyer: Mutations in CBL occur frequently in juvenile myelomonocytic leukemia. In: Blood. Vol-114, No. 9, August 2009, pp. 1859-1863, doi: 10.1182 / blood-2009-01-198416 , PMID 19571318 , PMC 2738571 (free full text).
2. ↑ ^{a b c d} 607785 JMML.  In: Online Mendelian Inheritance in Man . (English)
3. ↑ Ärzteblatt ( Memento of the original dated November 23, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 
4. ↑ ^{a b c} Rare Diseases
5. ↑ Juvenile myelomonocytic leukemia. In: Orphanet (Rare Disease Database).
6. ↑ Charlotte M Niemeyer, Michelle W Kang, Danielle H Shin, Ingrid Furlan, Miriam Erlacher, Nancy J Bunin, Severa Bunda, Jerry Z Finklestein, Kathleen M Sakamoto, Thomas A Gorr, Parinda Mehta, Irene Schmid, Gabriele Kropshofer, Selim Corbacioglu, Peter J Lang, Christoph Klein, Paul-Gerhard Schlegel, Andrea Heinzmann, Michaela Schneider, Jan Starý, Marry M van den Heuvel-Eibrink, Henrik Hasle, Franco Locatelli, Debbie Sakai, Sophie Archambeault, Leslie Chen, Ryan C Russell, Stephanie S. Sybingco, Michael Ohh, Benjamin S Braun, Christian Flotho, Mignon L Loh: Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. In: Nature Genetics. 42, 2010, p. 794, doi: 10.1038 / ng.641 .
7. ↑ CC Dvorak, ML Loh: Juvenile myelomonocytic leukemia: molecular pathogenesis informs current approaches to therapy and hematopoietic cell transplantation. In: Frontiers in pediatrics. Volume 2, 2014, p. 25, doi: 10.3389 / fped.2014.00025 , PMID 24734223 , PMC 3975112 (free full text) (review).

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