<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-04. The original page can be found at [[HAEM4:Pure Erythroid Leukemia]].
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Pure Erythroid Leukemia]].
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[1][2][3][4][5][6][7][8][9][10][11][12]. PEL is a distinct entity in the World Health Organization (WHO) classification system within the section of HAEM4: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)[1][2][3][4][5][6][7][8][9][10][11][12].
Synonyms / Terminology
Also known as AML-M6b and Di Guglielmo syndrome due to the recognition of the work of Di Guglielmo[1][2].
Epidemiology / Prevalence
PEL is extremely rare with a small number of reported cases, accounting for 3-5% of AML cases[1][2][10]. Median survival is usually three months[12].
Clinical Features
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Signs and Symptoms
EXAMPLE Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats)
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PEL has an aggressive clinical course with neoplastic proliferation of immature erythroid precursor (proerythroblastic or undifferentiated) cells. Average survival rate is three months[1][10]. PEL is characterized by neoplastic proliferation composed of >80% immature erythroid precursors of which proerythroblasts constitute ≥30%[12]. 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[1][10].
Sites of Involvement
Bone marrow, Blood
Morphologic Features
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[1]. Cells are usually negative for Myeloperoxidase (MPO) and Sudan Black (SBB). Bone marrow biopsy may have undifferentiated cells[1].
Immunophenotype
Differentiated PEL may express Glycophorin and hemoglobin A, absence of myeloperoxidase (MPO) and other myeloid markers[1]. Blasts are negative for HLA-Dr and CD34 but positive for CD117[1]. 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[1][12].
Finding
Marker
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
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
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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[1]. 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[10]. 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[11].
Karyotype of two year old boy with PEL[11]. FISH for ETV6 and RUNX1 in two year old boy with PEL[11]. FISH for EGR1 and D5S23,D5S721 (5p-) in two year old boy with PEL[11].
FISH for RB1 and 13q34 (13q deletion) in two year old boy with PEL[11].
Chromosomal Rearrangement
Genes in Fusion (5’ or 3’ Segments)
Pathogenic Derivative
Prevalence
t(1;16)(p31;q24)
5’NFIA/ 3’CBFA2T3
der(16)
Rare
t(11;20)(p11;q11)
5’MYND8/ 3’RELA
der(11)
Rare
editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).
Please incorporate this section into the relevant tables found in:
Chromosomal Rearrangements (Gene Fusions)
Individual Region Genomic Gain/Loss/LOH
Characteristic Chromosomal Patterns
Gene Mutations (SNV/INDEL)
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[3].
Individual Region Genomic Gain / Loss / LOH
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Chr #
Gain / Loss / Amp / LOH
Minimal Region Genomic Coordinates [Genome Build]
Minimal Region Cytoband
Diagnostic Significance (Yes, No or Unknown)
Prognostic Significance (Yes, No or Unknown)
Therapeutic Significance (Yes, No or Unknown)
Notes
EXAMPLE
7
EXAMPLE Loss
EXAMPLE
chr7:1- 159,335,973 [hg38]
EXAMPLE
chr7
Yes
Yes
No
EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
EXAMPLE
8
EXAMPLE Gain
EXAMPLE
chr8:1-145,138,636 [hg38]
EXAMPLE
chr8
No
No
No
EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference).
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Not Applicable
Chromosome Number
Gain/Loss/Amp/LOH
Region
5
Loss
Whole chromosome or q-arm
7
Loss
Whole chromosome or q-arm
8
Gain
Whole chromosome
17
Loss
P-arm
Characteristic Chromosomal Patterns
Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis)
Chromosomal Pattern
Diagnostic Significance (Yes, No or Unknown)
Prognostic Significance (Yes, No or Unknown)
Therapeutic Significance (Yes, No or Unknown)
Notes
EXAMPLE
Co-deletion of 1p and 18q
Yes
No
No
EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
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Gene Mutations (SNV / INDEL)
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JAK2, FLT3, RAS, NPM1, and CEBPA mutations have been reported to be rare in PEL[10][11][12]. 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[13].
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The molecular mechanism is not completely understood.
Genetic Diagnostic Testing Methods
Morphology and IHC.
Familial Forms
Not Applicable
Additional Information
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[1].
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↑ 1.001.011.021.031.041.051.061.071.081.091.101.111.12Arber DA, et al., (2008). World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p135-136.
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*Citation of this Page: “Acute erythroid leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/7/2023, https://ccga.io/index.php/HAEM5:Acute_erythroid_leukaemia.
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