Acute Lymphoblastic Leukaemia Flashcards
How does the expression of CD34, TDT, CD10, CD19, CD20, CD38 and CD45 change as haematogones mature?
CD34 decreases TDT decreases CD10 decreases CD19 increases CD20 increases CD38 decreases CD45 increases
What are some of the important markers used for COG MRD assessment in B-ALL?
Two tubes, six colours
CD45, CD19, CD10= backbone
CD38, CD58, CD20, CD9, CD34, CD13&CD33 (same fluorochrome) also used.
What is the LAIP approach? What are the advantages and disadvantages of this approach?
Combination of antigens expressed on the leukemic blasts at diagnosis that are absent in normal progenitors
Advantages:
- Able to reference the diagnostic immunophenotype of the blasts to asses for residual disease at set follow up points in treatment
Disadvantages:
- Immunophenotype of leukemic blasts alter following therapy due to subclonal selection or modulation of the immunophenotype.
- Immunophenotype of the background normal/ regenerating precursors may change their pattern of antigen expression in response to therapy
- Highly dependent on diagnostic immunophenotype, something that is not always available.
What is the DFN approach? What are the advantages and disadvantages of this approach?
Recognising immunophenotypic deviation from the patterns of antigen expression on normal hematopoietic progenitors
Advantages:
- Detection of leukemic blasts without knowledge of the diagnostic immunophenotype or after significant immunophenotypic changes.
- Implementation of a standard antibody panel containing both antigens commonly abnormal in leukemic cells as well as those emphasizing normal patterns of maturation.
Disadvantages:
- Requires expert knowledge of antigen expression patterns seen during differentiation and maturation of normal hematopoietic progenitors in resting and regeneration states, making standardization and implementation more challenging.
What is the current cut off used for MRD negativity post induction?
<0.01%
What does the term “MRD negative” imply?
That a technique with adequate sensitivity (≤10-4) has been used with proper technique on an adequate sample and that no residual disease was found at a set cut off point
What conditions are associated with an increased risk of ALL?
Down syndrome (20-30 fold risk) Ataxia telangiectasia Scwachman-Diamond syndrome Bloom syndrome Li Fraumeni syndrome
Discuss B-ALL with t(9;22)
- Increasing incidence with increasing age: 25% of adult ALL
- Typically, positive for CD10, TdT and CD19.
- Frequent expression of the myeloid antigens CD13, CD33. CD25 expression highly associated with BCR-ABL1 in adults.
- In most childhood cases: a p190 fusion protein is produced. In adults approximately 50% produce the p210 transcripts seen in CML.
- No definitive clinical differences between the two transcripts.
Discuss B-ALL with t(v;11q23)
- Large number of potential fusion partners. Most common= t(4;11)
- Most common cytogenetic abnormality in infants with ALL (i.e. <1 year).
- Only occurs in 1-2% of older children and then becomes increasingly common with age into adulthood.
- Characteristically positive for CD15 and CD65.
- Poor prognosis
Discuss B-ALL with t(12;21)
- Myeloid associated antigens, especially CD13 are frequently expressed.
- Favourable prognosis, cure seen in >90% of children.
- Relapses often occur much later than do those of other types of ALL
- Cytogenetically cryptic: diagnosed on FISH.
What is B-ALL with hyperdiploidy?
- Blasts contain >50 chromosomes (usually <66), typically without translocations or other structural variants.
- Increases of chromosome 21, X, 14 and 4 are the most common.
- Simultaneous trisomies involving 4 and 10 carry the best prognosis.
- Very favourable prognosis
What is B-ALL with hypodiploidy?
- Blasts contain <46 chromosomes.
- Three subtypes:
i. Near-haploid ALL (23- 29 chromosomes)
ii. Low hypodiploid (33- 39 chromosomes)
iii. High hypodiploid (40-43 chromosomes) - Low hypodiploid often associated with TP53 mutations (some of which are germline)
- Poor prognosis
Discuss Ph-like B-ALL
- Lack the BCR-ABL translocation but show a pattern of gene expression that is very similar to that seen in ALL with BCR-ABL1.
- Frequently harbour IKZF1 alterations (as seen in Ph B-ALL)
- Harbour a diverse range of genetic alterations including translocations involving tyrosine kinases (ABL1, JAK2, the JAK-STAT pathway), CRLF2 or less commonly rearrangements leading to truncation and activation of the EPO receptor (EPOR2).
- Relatively common entity with an incidence that peaks in young adults/ the AYA population
- Ph like ALL is overrepresented in high-risk ALL (even in children) and in those with Down syndrome (where the genetic lesion often involves CRLF2 translocations).
How is Ph like B-ALL diagnosed?
- Most centres will perform Ph like testing on those with who do not have recurrent cytogenetic abnormalities on the standard ALL FISH panel
- This can be performed by FISH or microarray
- Standard FISH panel for Ph like ALL:
CRLF2
JAK2
EPOR
CSF1R
ABL1
ABL2
PDGFRB - Those with CRLF2 translocations show high levels of surface expression of CRLF2 via flow cytometry which can be used to screen for this entity.
- Poor prognosis. Higher risk for MRD positivity
Discuss B-ALL with iAMP21
- Characterised by amplification of a portion of chromosome 21.
- Typically detected by FISH using a probe for the ETV6-RUNX1 translocation that reveals 5 or more copies of the gene (or 3 or more extra copies on a single chromosome).
- High rates of CRLF2 rearrangements.
