Pure Erythroid Leukemia
Ashwini Yenamandra PhD FACMG
- 1 Primary Author(s)*
- 2 Cancer Category/Type
- 3 Cancer Sub-Classification / Subtype
- 4 Definition / Description of Disease
- 5 Synonyms / Terminology
- 6 Epidemiology / Prevalence
- 7 Clinical Features
- 8 Sites of Involvement
- 9 Morphologic Features
- 10 Immunophenotype
- 11 Chromosomal Rearrangements (Gene Fusions)
- 12 Characteristic Chromosomal Aberrations / Patterns
- 13 Genomic Gain/Loss/LOH
- 14 Gene Mutations (SNV/INDEL)
- 15 Epigenomics (Methylation)
- 16 Genes and Main Pathways Involved
- 17 Diagnostic Testing Methods
- 18 Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
- 19 Familial Forms
- 20 Other Information
- 21 Links
- 22 References
- 23 Notes
Cancer Sub-Classification / Subtype
Pure Erythroid Leukemia (PEL) is now the only type of Acute Erythroid Leukemia (AEL).
Definition / Description of Disease
In the 2008 WHO classification, Acute Erythroid leukemia (AEL) was classified into two subtypes: Erythroleukemia (erythroid/myeloid) and Pure Erythroid Leukemia (PEL). However, in the 2016 WHO update, Erythroleukemia was merged into myelodysplastic syndrome, while PEL is now the only type of AEL. PEL is a distinct entity in the World Health Organization (WHO) classification system within the section of Acute Myeloid Leukemia (AML), Not Otherwise Specified. PEL is a rare form of acute leukemia with an aggressive clinical course and is characterized by an uncontrolled proliferation of immature erythroid precursors (proerythroblastic or undifferentiated).
Synonyms / Terminology
Epidemiology / Prevalence
PEL has an aggressive clinical course with neoplastic proliferation of immature erythroid precursor (proerythroblastic or undifferentiated) cells. Average survival rate is three months. PEL is characterized by neoplastic proliferation composed of >80% immature erythroid precursors of which proerythroblasts constitute ≥30%. Clinical features include profound anemia, circulating erythroblasts, pancytopenia, extensive bone marrow involvement, fatigue, infections, weight loss, fever, night sweats, hemoglobin level under 10.0 g/dL, and thrombocytopenia.
Sites of Involvement
Bone marrow, Blood
PEL is characterized by medium to large erythroblasts with round nuclei, fine chromatin and one or more nucleoli (proerythroblast). Cytoplasm is deeply basophilic, often granular with demarcated vacuoles and are often Periodic-Acid-Schiff stain (PAS) positive. Blasts can be small and may resemble lymphoblasts. Cells are usually negative for Myeloperoxidase (MPO) and Sudan Black (SBB). Bone marrow biopsy may have undifferentiated cells.
Differentiated PEL may express Glycophorin and hemoglobin A, absence of myeloperoxidase (MPO) and other myeloid markers. Blasts are negative for HLA-Dr and CD34 but positive for CD117. Immature forms can be negative for Glycophorin or weekly expressed. Positive for Carbonic anhydrase 1, Gero antobody against the Gerbich blood group or CD36 especially at earlier stages of differentiation. CD41 and CD61 are negative.
|Positive (universal)||Hemoglobin A, Glycophorin A, Spectrin, ABH blood group antigens, and HLA-DR|
|Positive (subset)||CD13, CD33, CD34, CD117 (KIT), and MPO, Gerbich blood group (Gero) antibody, carbonic anhydrase 1, and CD36, CD41 and CD61|
|Negative (universal)||Myeloid-associated markers such as MPO,CD13,CD33,CD61, B and T Cell markers -CD10, CD19, CD79a, CD2, CD3, CD5, monocytic markers CD11c CD14
Megakaryoblastic markers: CD61, Others: CD34, anti-kappa, anti-lambda, CD45
|Negative (subset)||HLA-DR, CD34, Glycophorin A|
Chromosomal Rearrangements (Gene Fusions)
The genetic abnormalities that have been identified in PEL are similar to that of AML and MDS and consists of complex chromosomal abnormalities including -5/del(5q), -7/del(7q), +8 and/or RUNX1 and TP53 mutations. Rearrangement of NFIA-CBFA2T3 with t(1;16)(p31;q24) and MYND8-RELA with t(11;20)(p11;q11) have been reported in rare cases. A complex karyotype with 46,XY,der(5)del(5)(p15.1p15.1)t(5;12;7)(p15.1;p13;q32),der(7)t(5;12;7),der(12)del(12)p13p13)t(5;12;7),del(13)(q12q14) was reported in a two year old boy with PEL.
|Chromosomal Rearrangement||Genes in Fusion (5’ or 3’ Segments)||Pathogenic Derivative||Prevalence|
Characteristic Chromosomal Aberrations / Patterns
|5||Loss||Whole chromosome or q-arm|
|7||Loss||Whole chromosome or q-arm|
Gene Mutations (SNV/INDEL)
JAK2, FLT3, RAS, NPM1, and CEBPA mutations have been reported to be rare in PEL. Intraclonal heterogeneity and founder mutations of TP53 were reported in 92% (11 out of 12 cases) while co-occurrence of TP53 mutation and deletion due to chromosome 17p abnormalities were detected in 73% of PEL cases.
|Gene||Mutation||Oncogene/Tumor Suppressor/Other||Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)||Prevalence (COSMIC/TCGA/Other)|
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%|
|Concomitant Mutations||EXAMPLE IDH1 R123H|
|Secondary Mutations||EXAMPLE Trisomy 7|
|Mutually Exclusive||EXAMPLE EGFR Amplification|
Genes and Main Pathways Involved
The molecular mechanism is not completely understood.
Diagnostic Testing Methods
Morphology and IHC.
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
PEL has rapid and aggressive clinical course. Patients with PEL are treated similar to other types of AML. Stem cell transplantation (SCT) may have an improvement in the outcome of the disease. No therapeutic agents for specific target pathways are currently available.
Differential Diagnosis: PEL without morphological differentiation of erythroid maturation can be difficult to distinguish from megakaryoblastic leukemia (AML), ALL or lymphoma. The erythroid precursor immunophenotype helps in the diagnosis. Some cases can be complex with concurrent erythroid megakaryocytic involvement.
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