U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Juvenile myelomonocytic leukemia(JMML)

MedGen UID:
138109
Concept ID:
C0349639
Neoplastic Process
Synonyms: JMML; LEUKEMIA, JUVENILE MYELOMONOCYTIC, SOMATIC
SNOMED CT: Juvenile chronic myelomonocytic leukemia (128832006); Juvenile myelomonocytic leukemia (128832006); Juvenile myelomonocytic leukemia (445227008); JCML - Juvenile chronic myeloid leukemia (277587001); Juvenile chronic myeloid leukemia (277587001)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Genes (locations): ARHGAP26 (5q31.3); CBL (11q23.3); NF1 (17q11.2); PTPN11 (12q24.13)
 
HPO: HP:0012209
Monarch Initiative: MONDO:0011908
OMIM®: 607785
Orphanet: ORPHA86834

Definition

Juvenile myelomonocytic leukemia is an aggressive pediatric myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD) characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny (Loh et al., 2009). JMML constitutes approximately 30% of childhood cases of myelodysplastic syndrome and 2% of leukemia (Hasle et al., 1999). Although JMML is a progressive and often rapidly fatal disease without hematopoietic stem cell transplantation (HSCT), some patients have been shown to have a prolonged and stable clinical course without HSCT (Niemeyer et al., 1997). Chronic myelomonocytic leukemia (CMML) is a similar disorder with later onset. Both JMML and CMML have a high frequency of mutations affecting the RAS signaling pathway and show hypersensitivity to stimulation with GM-CSF, which causes STAT5 (601511) hyperphosphorylation (Loh et al., 2009). Genetic Heterogeneity of Juvenile Myelomonocytic Leukemia In up to 60% of cases of JMML, the RAS/MAPK pathway is deregulated due to somatic mutations in the PTPN11 (176876), KRAS (190070), and NRAS (164790) genes. Additionally, both germline and somatic mutations in the CBL gene have been found in patients with JMML, indicating a frequency of 10 to 15% of JMML patients overall (Loh et al., 2009). Somatic disruptions of the GRAF gene (ARHGAP26; 605370) have also been found in patients with JMML. About 10 to 15% of JMML cases arise in children with neurofibromatosis type I (NF1; 162200) due to germline mutations in the NF1 gene (613113). In addition, patients with Noonan syndrome (NS1, 163950; NS3, 609942) or Noonan syndrome-like disorder (NSLL; 613563) due to germline mutations in the PTPN11, KRAS2, and CBL genes, respectively, also have an increased risk of developing JMML. Genetic Heterogeneity of Chronic Myelomonocytic Leukemia Somatic mutations in the CBL, ASXL1 (612990), TET2 (612839), and SF3B1 (605590) genes have been found in patients with CMML. [from OMIM]

Clinical features

From HPO
Juvenile myelomonocytic leukemia
MedGen UID:
138109
Concept ID:
C0349639
Neoplastic Process
Juvenile myelomonocytic leukemia is an aggressive pediatric myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD) characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny (Loh et al., 2009). JMML constitutes approximately 30% of childhood cases of myelodysplastic syndrome and 2% of leukemia (Hasle et al., 1999). Although JMML is a progressive and often rapidly fatal disease without hematopoietic stem cell transplantation (HSCT), some patients have been shown to have a prolonged and stable clinical course without HSCT (Niemeyer et al., 1997). Chronic myelomonocytic leukemia (CMML) is a similar disorder with later onset. Both JMML and CMML have a high frequency of mutations affecting the RAS signaling pathway and show hypersensitivity to stimulation with GM-CSF, which causes STAT5 (601511) hyperphosphorylation (Loh et al., 2009). Genetic Heterogeneity of Juvenile Myelomonocytic Leukemia In up to 60% of cases of JMML, the RAS/MAPK pathway is deregulated due to somatic mutations in the PTPN11 (176876), KRAS (190070), and NRAS (164790) genes. Additionally, both germline and somatic mutations in the CBL gene have been found in patients with JMML, indicating a frequency of 10 to 15% of JMML patients overall (Loh et al., 2009). Somatic disruptions of the GRAF gene (ARHGAP26; 605370) have also been found in patients with JMML. About 10 to 15% of JMML cases arise in children with neurofibromatosis type I (NF1; 162200) due to germline mutations in the NF1 gene (613113). In addition, patients with Noonan syndrome (NS1, 163950; NS3, 609942) or Noonan syndrome-like disorder (NSLL; 613563) due to germline mutations in the PTPN11, KRAS2, and CBL genes, respectively, also have an increased risk of developing JMML. Genetic Heterogeneity of Chronic Myelomonocytic Leukemia Somatic mutations in the CBL, ASXL1 (612990), TET2 (612839), and SF3B1 (605590) genes have been found in patients with CMML.

Conditions with this feature

Juvenile myelomonocytic leukemia
MedGen UID:
138109
Concept ID:
C0349639
Neoplastic Process
Juvenile myelomonocytic leukemia is an aggressive pediatric myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD) characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny (Loh et al., 2009). JMML constitutes approximately 30% of childhood cases of myelodysplastic syndrome and 2% of leukemia (Hasle et al., 1999). Although JMML is a progressive and often rapidly fatal disease without hematopoietic stem cell transplantation (HSCT), some patients have been shown to have a prolonged and stable clinical course without HSCT (Niemeyer et al., 1997). Chronic myelomonocytic leukemia (CMML) is a similar disorder with later onset. Both JMML and CMML have a high frequency of mutations affecting the RAS signaling pathway and show hypersensitivity to stimulation with GM-CSF, which causes STAT5 (601511) hyperphosphorylation (Loh et al., 2009). Genetic Heterogeneity of Juvenile Myelomonocytic Leukemia In up to 60% of cases of JMML, the RAS/MAPK pathway is deregulated due to somatic mutations in the PTPN11 (176876), KRAS (190070), and NRAS (164790) genes. Additionally, both germline and somatic mutations in the CBL gene have been found in patients with JMML, indicating a frequency of 10 to 15% of JMML patients overall (Loh et al., 2009). Somatic disruptions of the GRAF gene (ARHGAP26; 605370) have also been found in patients with JMML. About 10 to 15% of JMML cases arise in children with neurofibromatosis type I (NF1; 162200) due to germline mutations in the NF1 gene (613113). In addition, patients with Noonan syndrome (NS1, 163950; NS3, 609942) or Noonan syndrome-like disorder (NSLL; 613563) due to germline mutations in the PTPN11, KRAS2, and CBL genes, respectively, also have an increased risk of developing JMML. Genetic Heterogeneity of Chronic Myelomonocytic Leukemia Somatic mutations in the CBL, ASXL1 (612990), TET2 (612839), and SF3B1 (605590) genes have been found in patients with CMML.
Noonan syndrome 3
MedGen UID:
349931
Concept ID:
C1860991
Disease or Syndrome
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.
Noonan syndrome 6
MedGen UID:
413028
Concept ID:
C2750732
Disease or Syndrome
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.
CBL-related disorder
MedGen UID:
462153
Concept ID:
C3150803
Disease or Syndrome
Noonan syndrome-like disorder is a developmental disorder resembling Noonan syndrome (NS1; 163950) and characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, and ectodermal and musculoskeletal anomalies. There is extensive phenotypic heterogeneity and variable expressivity (summary by Martinelli et al., 2010). Patients with heterozygous germline CBL mutations have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia (JMML; 607785), as also seen in patients with Noonan syndrome (summary by Niemeyer et al., 2010).
Noonan syndrome 1
MedGen UID:
1638960
Concept ID:
C4551602
Disease or Syndrome
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.

Professional guidelines

PubMed

Liao XY, Qiu KY, Fang JP, Wu RH, Guo SY, Huang K, Zhou DH
Hematology 2019 Dec;24(1):577-582. doi: 10.1080/16078454.2019.1651548. PMID: 31389303
Locatelli F, Algeri M, Merli P, Strocchio L
Expert Rev Hematol 2018 Feb;11(2):129-143. Epub 2018 Jan 3 doi: 10.1080/17474086.2018.1421937. PMID: 29279013
Sakashita K, Matsuda K, Koike K
Pediatr Int 2016 Aug;58(8):681-90. doi: 10.1111/ped.13068. PMID: 27322988

Recent clinical studies

Etiology

Rudelius M, Weinberg OK, Niemeyer CM, Shimamura A, Calvo KR
Virchows Arch 2023 Jan;482(1):113-130. Epub 2022 Nov 29 doi: 10.1007/s00428-022-03447-9. PMID: 36445482
Patnaik MM
Haematologica 2022 Jul 1;107(7):1503-1517. doi: 10.3324/haematol.2021.279500. PMID: 35236051Free PMC Article
Brown PA
Clin Perinatol 2021 Mar;48(1):15-33. doi: 10.1016/j.clp.2020.11.002. PMID: 33583502
Neven Q, Boulanger C, Bruwier A, de Ville de Goyet M, Meyts I, Moens L, Van Damme A, Brichard B
J Clin Immunol 2021 Jan;41(1):51-58. Epub 2020 Oct 4 doi: 10.1007/s10875-020-00883-7. PMID: 33011939
Galanello R, Origa R
Orphanet J Rare Dis 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11. PMID: 20492708Free PMC Article

Diagnosis

Rudelius M, Weinberg OK, Niemeyer CM, Shimamura A, Calvo KR
Virchows Arch 2023 Jan;482(1):113-130. Epub 2022 Nov 29 doi: 10.1007/s00428-022-03447-9. PMID: 36445482
Patnaik MM
Haematologica 2022 Jul 1;107(7):1503-1517. doi: 10.3324/haematol.2021.279500. PMID: 35236051Free PMC Article
Patnaik MM, Lasho TL
Hematology Am Soc Hematol Educ Program 2020 Dec 4;2020(1):450-459. doi: 10.1182/hematology.2020000130. PMID: 33275756Free PMC Article
Seth R, Singh A
Indian J Pediatr 2015 Sep;82(9):817-24. Epub 2015 Feb 15 doi: 10.1007/s12098-015-1695-5. PMID: 25680783
Galanello R, Origa R
Orphanet J Rare Dis 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11. PMID: 20492708Free PMC Article

Therapy

Pasupuleti SK, Chao K, Ramdas B, Kanumuri R, Palam LR, Liu S, Wan J, Annesley C, Loh ML, Stieglitz E, Burke MJ, Kapur R
Mol Ther 2023 Apr 5;31(4):986-1001. Epub 2023 Feb 3 doi: 10.1016/j.ymthe.2023.01.030. PMID: 36739480Free PMC Article
Patnaik MM, Lasho T
Hematology Am Soc Hematol Educ Program 2020 Dec 4;2020(1):460-464. doi: 10.1182/hematology.2020000163. PMID: 33275673Free PMC Article
Locatelli F, Algeri M, Merli P, Strocchio L
Expert Rev Hematol 2018 Feb;11(2):129-143. Epub 2018 Jan 3 doi: 10.1080/17474086.2018.1421937. PMID: 29279013
Yoshimi A, Kojima S, Hirano N
Paediatr Drugs 2010;12(1):11-21. doi: 10.2165/11316200-000000000-00000. PMID: 20034338
Aricò M, Biondi A, Pui CH
Blood 1997 Jul 15;90(2):479-88. PMID: 9226148

Prognosis

Patnaik MM
Haematologica 2022 Jul 1;107(7):1503-1517. doi: 10.3324/haematol.2021.279500. PMID: 35236051Free PMC Article
Neven Q, Boulanger C, Bruwier A, de Ville de Goyet M, Meyts I, Moens L, Van Damme A, Brichard B
J Clin Immunol 2021 Jan;41(1):51-58. Epub 2020 Oct 4 doi: 10.1007/s10875-020-00883-7. PMID: 33011939
Patnaik MM, Lasho TL
Hematology Am Soc Hematol Educ Program 2020 Dec 4;2020(1):450-459. doi: 10.1182/hematology.2020000130. PMID: 33275756Free PMC Article
Patnaik MM, Lasho T
Hematology Am Soc Hematol Educ Program 2020 Dec 4;2020(1):460-464. doi: 10.1182/hematology.2020000163. PMID: 33275673Free PMC Article
Galanello R, Origa R
Orphanet J Rare Dis 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11. PMID: 20492708Free PMC Article

Clinical prediction guides

Pasupuleti SK, Chao K, Ramdas B, Kanumuri R, Palam LR, Liu S, Wan J, Annesley C, Loh ML, Stieglitz E, Burke MJ, Kapur R
Mol Ther 2023 Apr 5;31(4):986-1001. Epub 2023 Feb 3 doi: 10.1016/j.ymthe.2023.01.030. PMID: 36739480Free PMC Article
Patnaik MM
Haematologica 2022 Jul 1;107(7):1503-1517. doi: 10.3324/haematol.2021.279500. PMID: 35236051Free PMC Article
Patel AB, Deininger MW
Leuk Lymphoma 2021 May;62(5):1031-1045. Epub 2020 Dec 18 doi: 10.1080/10428194.2020.1856837. PMID: 33337259
Niemeyer CM, Flotho C
Blood 2019 Mar 7;133(10):1060-1070. Epub 2019 Jan 22 doi: 10.1182/blood-2018-11-844688. PMID: 30670449
Niemeyer CM
Hematology Am Soc Hematol Educ Program 2018 Nov 30;2018(1):307-312. doi: 10.1182/asheducation-2018.1.307. PMID: 30504325Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...