Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Hematopathology WHO > B-Lymphoblastic Leukemia/Lymphoma with Recurrent Genetic Abnormalities > Flashcards

B-Lymphoblastic Leukemia/Lymphoma with Recurrent Genetic Abnormalities Flashcards

1
Q

What is the definition of B-ALL with

t(9;22)(q34.1;q11.2), BCR-ABL1 ?

A
  • specific type of B-ALL where the blasts harbor the BCR-ABL1 translocation
    • BCR on chromosome 22
    • ABL1 on chromsome 9
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the epidemiology of t(9;22) B-ALL ?

A
  • relatively more common in adults than in children
    • account for ~25% of adult ALL
    • only 2-4% of childhood cases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the clinical features of B-ALL with BCR-ABL1 ?

A
  • similar to those seen in B-ALL NOS
  • in children they are high risk based on age and white blood cell count
  • there may be organ involvement with this subtype but lymphomatous presentations are rare
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the immunophenotype of B-ALL

with BCR-ABL1 ?

A
  • the histology is not unique and looks like other B-ALL
  • Immunophenotype
    • positive for: CD10, CD19, and TdT
    • frequently positive for CD13, CD33 but should be negative for CD117
  • IMP
    • CD25 positivity is associated with BCR-ABL in adults

Note: rare cases of ALL with BCR-ABL1 have a T-cell precursor phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the cell of origin for B-ALL

with BCR-ABL1 ?

A
  • some evidence that this cell of origin is more immature than that of other B-ALL cases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the key genetic findings/features of

B-ALL with t(9;22) ?

A
  • t(9;22)
    • occurs from fusion of BCR at 22q11.2 and the cytoplasmic tyrosine kinas ABL1 at 9q34.1
  • childhood cases
    • p190 fusion is produced
  • adult cases
    • about half the cases produce p210 fusion protein similar to CML
    • while the remainder produce p190
  • No clinical differences are attributed to the different gene products
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the prognosis and predictive

factors for B-ALL with BCR-ABL1 ?

A
  • both in children and adults, B-ALL with BCR-ABL1 is thought to have the worst prognosis of the major cytogenetic subtypes
    • this is partially due to the fact that it is more common in adults
  • Favorable clinical featues in kids include:
    • younger age
    • lower WBC count
    • response to therapy
  • IMP
    • treatment with TKIs has had a signifiant favorable outcome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the definition of B-ALL with

t(v;11q23.3) or KMT2A rearrangement ?

A
  • blasts harbor translocation between KMT2A (MLL) at band 11q23.3
    • there can be many different fusion partners
    • break apart probe by FISH

IMP: leukemias that have deletions of 11q23.2 without KMT2A rearrangement are not included in this group.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the epidemiology of B-ALL

with KMT2A rearrangement ?

A
  • most common leukemia in infants aged <1 year old
  • less common in older children
    • increases in incidence with increasing age into adulthood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the etiology of B-ALL with KMT2A rearrangement ?

A
  • etiology is truly unknown
  • KMT2A translocations can occur in utero with a short latency between the translocation and development of the malignancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the clinical features of B-ALL

with KMT2A ?

A
  • usually patients present with a very high WBC
    • > 100 x10^9/L
  • also very high frequency of CNS involvement
  • organ involvement may be seen
    • but pure lymphomatous presentations are not typical
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are characteristic findings on microscopy

in B-ALL with KMT2A ?

A
  • no unique morphological or cytochemical findings
  • IMP
    • in some cases it is possible to distinguish a lymphoblastic and monoblastic population
    • but in these cases, it should be called a B/Myeloid leukemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the immunophenotype of B-ALL

with KMT2A ?

A
  • for cases with the t(4;11)
    • CD19+, CD10-, CD24-
    • CD15+
    • pro-B immunophenotype
    • also the NG2 homologue encoded by CSPG4 is also characteristically expressed and is relatively specific
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the genetic profile seen in B-ALL with

KMT2A ?

A
  • KMT2A gene is on chromosome 11q.23.3 and it is a very promiscuous oncogene
  • > 100 fusion partners
  • translocations can be identified by:
    • standard karyotype
    • FISH with break apart probe
    • PCR for major translocation partners but a negative result would not exclude any translocations
  • Leukemias with KMT2A are often associated with overexpression of FLT3.
  • B-ALL with KMT2A has very few associated additional mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the major translocations partners

of KMT2A ?

A
  • AFF1 (AF4)- most common partner, chromosome 4q21
  • Other partner genes
    • MLLT1 ( chromosome 19p13.3)
      • fusion with this gene is also seen inT-ALL
    • MLLT3 (chromosome 9p21.3)
      • fusion with this gene are also commonly seen in AML
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the prognosis and predictive

factors for B-ALL with KMT2A ?

A
  • KMT2A-AFF1 - poor prognosis
  • Debate about if other KMT2A translocations also have poor prognosis
  • infants. < 6 months have a particularly poor prognosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the epidemiology and clinical features of B-ALL with

t(12;21)(p12.2;q22.1)// ETV6-RUNX1 ?

A
  • this B-ALL is NOT seen in infants
  • most frequent in children
    • 25% of all cases
    • decreases in frequency with age
    • rare in adulthood
  • Clinical features are the same as other B-ALL
  • Also no unique morphological or cytochemical features
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the immunophenotype for

B-ALL with ETV6-RUNX1 ?

A
  • positive for CD19, CD10 and CD34 (usually)
  • complete absence of CD9, CD20 and CD66c are relatively specific
  • CD13 (myeloid associated antigen)
    • frequently expressed
  • it is thought this derives from a B-cell progenitor rather than a stem cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is another name for ETV6-RUNX1 ?

A
  • TEL/AML1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the key genetic considerations in

B-ALL with ETV6-RUNX1 ?

A
  • the fusion protein is thought to interfere with normal function of the transciption factor RUNX1
  • considered to be an early lesion in leukemogenesis but alone is not sufficient to cause leukemia
  • demonstrated by fusion FISH probes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the prognostic and predictive factors

of B-ALL with ETV6-RUNX1 ?

A
  • favorable prognosis
    • cure rate of. >90%
  • relapses occur much later than other types of ALL
  • children with adverse prognostic factors such as:
    • age >10 years
    • high WBC count
    • do not have as good of a prognosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the definition of

B-ALL with hyperdiploidy ?

A
  • leukemia whose blasts contain > 50 chromsomes but < 66
  • typically without translocations or other alterations
  • debate about whether specific extra chromsomes should be part of the definition or just extra chromosomes in general
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the epidemiology of B-ALL

with hyperdiploidy ?

A
  • common in children and accounts for ~25% of cases
  • NOT seen in infants
    • decreases in frequency among older children
  • uncommon in adults
    • 8% of cases
  • Clinical features are generally similar to those of other ALL
  • No unique features on microscopy
24
Q

What is the immunophenotype of B-ALL

with hyperdiploidy ?

A
  • CD19 and CD10 positive
  • CD34 is positive in most cases and CD45 is usually negative
25
Q

What are the specific genetic considerations in

B-ALL with hyperdiploidy ?

A
  • B-ALL with extra chromosomes
  • The chromosomes are NOT random
    • 21, X, 14 and 4 are the most commonly seen
    • 1, 2, and 3 are the least common seen
  • These can be detected by conventional karyotyping, FISH or flow cytometric DNA index
    • CAUTION: some cases by karyotype of hyperdiploid ALL may actually be hypodiploid that has undergone endoreduplication (doubling of chromsomes)
  • Chromsomes 4 and 10
    • carry the best prognosis
26
Q

What are the prognosis and predictive

factors of hyperdiploid B-ALL ?

A
  • very favorable prognosis with cure rates seen in >90% of cases
  • even in children with adverse prognostic features
    • advanced patient age
    • high WBC count
  • too few adults have been studied with this to determine prognosis
27
Q

What is the definition of hypodiploid B-ALL ?

A
  • blasts contain <46 chromosomes
  • Three (sometimes 4 categories)
    • near haploid ALL (23-29 chromosomes)
    • low hypodiploid (33-39 chromosomes)
    • high hypodiploid (40-43 chromsomes)
  • Fourth category sometimes seen
    • near diploid ALL (44-45 chromsomes)
    • not included at least for treatment purposes because they do not share the poor prognostic features of the other 3 categories
28
Q

What is the epidemiology of hypodiploid

B-ALL ?

A
  • about 5% of all ALL cases
    • but if you restrict the definition to <45 chromosomes it accounts for only 1% of all cases
  • occurs in both children and adults
    • but near-haploid ALL (23-29 chromosomes) is mostly seen in children
  • No unique clinical or morphologic features
  • No unique immunophenotype
29
Q

What are key considerations in the genetic

profile of hypodiploid B-ALL ?

A
  • structural abnormalities can be present in the remaining chromosomes (though none are specific)
    • but nearly never seen in near-haploid ALL
  • Near-haploid ALL can be missed by karyotyping
    • due to endoreduplication
    • generally flow and FISH will show chromosomes that are hypodiploid or DNA <1 (flow)
30
Q

What is the distinct genetic lesion

associated with near-haploid ALL ?

A
  • RAS or receptor tyrosine kinase mutations
31
Q

What are the distinctive genetic lesions

associated with low hypodiploid ALL ?

A
  • most distinctive class
  • loss of function mutations in TP53 and RB1
    • some of the TP53 mutations are germline
      • suggests a form of Li Fraumeni syndrome

IMP: these lesions do not occur with high hypodiploid ALL

  • it does not have any specific gene alterations
32
Q

What are the prognosis and predictive

factors for hypodiploid ALL ?

A
  • poor prognosis
    • near haploid ALL having the worst prognosis

IMP: in this category there is some evidence that even if there is no MRD after treatment these patients still fair poorly

33
Q

What is the definition of B-ALL with

t(5;14)(q31.1;q32.1), IGH-IL3 ?

A
  • blasts harbor a translocation between IL3 and IGH gene
  • results in variable eosinophilia
  • this diagnosis can be made based on the genetics even if the bone marrow blast percentage is low
34
Q

What is the epidemiology and clinical features of B-ALL with

IL-3-IGH t(5;14) ?

A
  • very rare ALL, <1% of all cases
  • occurs in both kids and adults
  • clinical features are similar with the exception of asymptomatic eosinophilia
    • blasts may be absent from the PB
35
Q

What are the microscopic and immunophenotypic

findings of B-ALL with IL-3-IGH ?

A
  • blasts have the typical morphology
  • marked eosinophilia is associated with this neoplasm
    • eos are reactive and not part of the clone **
  • blasts have the usual CD19+ and CD10+ immunophenotype
36
Q

What are the genetic considerations for

B-ALL with IL-3/IGH ?

A
  • IL3 gene is on chromosome 5
  • IHG gene is on chromosome 14
  • other than eosinophilia the functional consequences of this rearrangement are not completely understood
  • Can be detected by:
    • conventional karyotype
    • FISH
      • but the probes are not widely available
37
Q

What are the prognostic and predictive

factors for B-ALL with IL-3/IGH ?

A
  • prognosis is not thought to be different than other types of ALL
    • but there are really too few cases to be certain
  • blast percentage at diagnosis is not known to be a predictive factor
38
Q

What is the definition of B-ALL with t(1;19)(q23;p13.3)

TCF3-PBX1 ?

A
  • this is a translocation between TCF3 (also known as E2A on chromosome 19 and PBX1 on chromosome 1
39
Q

What is the etiology, clinical and microscopic

features of B-ALL with t(1;19) ?

A
  • this translocation is relatively common in children
    • accounts for about 6% of cases of B-ALL
  • it is less common in adults
  • clinical features are the same
  • microscopic features are the same
40
Q

What is the immunophenotype of the

blasts in B-ALL with

t(1;19) ?

A
  • blasts typically have a pre-B phenotype
    • positive for CD19, CD10 and cytoplasmic mu chain
  • IMP
    • not all cases of pre-B-ALL have the t(1;19)
  • diagnosis can be suspected even if cytoplasmic mu is not detected
  • leukemias show
    • strong expression of CD9
    • lack CD34 or very little CD34 on a minor portion of leukemic cells
41
Q

What is the genetic profile for B-ALL with

t(1;19) ?

A
  • this oncogenic fusion protein interferes with normal function of the transcription factors coded by TCF3 and PBX1
  • this is a unique lesion identified by gene expression profiling
  • Alternative translocation:
    • t(17;19) TCF3 with HLF
    • associated with dismal prognosis
  • IMP:
    • a subset of B-ALL cases, hyperdiploid type, have a karyotype identical to t(1;19) that does not involve either TCF3 or PBX1
    • these entities should not be considered the same
42
Q

What are the prognosis and predictive factors

for B-ALL with t(1;19), TCF3-PBX1 ?

A
  • in early studies it was associated with a poor prognosis, but with modern intensive therapy they do ok
  • BUT
    • increased relative risk of CNS relapse
43
Q

What is the definition of B-ALL,

BCR-ABL1- like ?

A
  • lack BCR-ABL1 translocation but by gene expression profiling show a similar pattern to those with the BCR-ABL1 translocation
  • Often have translocations affecting other tyrosine kinases:
  • alternative translocations involving CRLF2
  • less commonly, rearrangements leading to truncation and activation of the EPO receptor
44
Q

What is the epidemiology of B-ALL with

BCR-ABL1-like ?

A
  • this leukemia is relatively common, 10-25% of ALL patients
    • progressively higher incidence in kids with high risk ALL, adolescents and adults
  • Down Syndrome kids
    • very high frequency of ALL with CRLF2 translocation
  • Frequency of some genomic alterations vary with ethnicity
    • IGH/CRLF2
      • more comon in hispanics and Native Americans
45
Q

What is the etiology of

BCR-ABL1-like B-ALL ?

A
  • no definitive details on etiology
  • certain inherited GATA3 variants confer an increased risk of this entity
46
Q

What are the clinical and microscopic findings

of BCR-ABL1-like B-ALL ?

A
  • generally similar clinical presentation
    • tend to havce higher WBC counts
  • No unique morphologic or cytochemical features
47
Q

What is the immunophenotype of

BCR-ABL1-like B-ALL ?

A
  • Blasts usually have a CD19+ CD10+ phenotype
  • CRLF2 translocation cases
    • can show very high levels of expression of the protein by flow cytometry
    • can be used to screen for cases with this translocation
  • No specific immunophenotypic features for cases with translocations involving EPOR or tyrosine kinases
48
Q

What are the key considerations for the

genetic profile for BCR-ABL1 like B-ALL ?

A
  • show various types of chromosomal rearrangements
    • involve many genes and gene partners
  • CRLF2 rearrangments
    • account for 1/2 the cases
    • often show an interstitial deletion of PAR1 family gene on Xp22.3 and Yp11.3
      • this juxtaposes CRLF2 to the promoter of the P2RY8 gene
      • also an alternative translocation involving IGH
49
Q

What is true regarding the alternative tyrosine kinase type

translocations in BCR-ABL1-like B-ALL ?

A
  • reported to involve ABL1 with partners other than BCR
  • more than 30 partner genes have been described
  • Kinase translocations only rarely exist with CRLF2 rearrangements
50
Q

What modalities can be used to detect genetic alterations

in BCR-ABL1-like B-ALL ?

A
  • some can be detected by standard karyotype but many are cryptic
    • particularly those involving the interstitial deletion of CRLF2
  • Also many cases show deletions or mutations in other genes known to be important in leukemogenesis
    • IKZF1
    • CDKN2A/B
  • IMP
    • about 1/2 the cases with CRLF2 rearranged ALL show mutations in JAK2 or JAK1
51
Q

What are the prognosis and predictive factors for

BCR-ABL1-like B-ALL ?

A
  • overall poor prognosis
  • higher risk of positive MRD
  • CRLF2 translocations have specifically been associated with poor outcomes
  • Resistance to induction chemotherapy has been most frequently seen with:
    • translocations between PDGFRB and EBF1
      • these patients respond to TKIs like Imatinib
52
Q

What is the definition of B-ALL with

iAMP21 ?

A
  • amplification of a portion of chromosome 21
  • typically detected by FISH
    • probe is for RUNX1
    • shows >5 copies of the gene or
    • >3 extra copies on a single abnormal chromosome 21
53
Q

What is the epidemiology of

B-ALL with iAMP21 ?

A
  • low incidence, 2% of cases in children
    • uncertain about incidence in adults
  • more common in older children who present with lower WBC counts
54
Q

What is the etiology, clinical features and microscopic

findings of B-ALl with iAMP21 ?

A
  • not sure but people with rare constitutional Robertsonian translocation rob(15;21)
    • 3000 fold risk of developing leukemia
  • no unique clinical or morphologic features
55
Q

What are the important genetic considerations

in B-ALL with iAMP21 ?

A
  • disease is detected with FISH probes against ETV6-RUNX1 but the disease does not involve pathogenesis of RUNX1
  • in 20% of cases this is the only abnormality
    • many other chromosome abnormalities are seen, most common include:
      • gains of chromsome X and abnormalities of chromosome 7
    • also associated with deletions of RB1 and ETV6, also have rearrangments of CRLF2 (greater frequency than other ALLs)
    • IMP: role of all these alterations is uncertain
56
Q

What are the prognostic and predictive

factors of B-ALL with iAMP21 ?

A
  • relatively poor prognosis among kids
    • but it is militated with more intensive chemotherapy
57
Q
A

Hematopathology WHO (29 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions