Chronic Myeloid Neoplasms

Question 1

Five overall categories of chronic myeloid neoplasms

Answer 1

Myelodysplastic syndromes
Myeloproliferative neoplasms
MDS/MPN overlap syndromes
Mastocytosis
Myeloid neoplasms associated with eosinophilia and abnormalities of PDGFR(A or B) or FGFR1

Question 2

MPN-category chronic myeloid neoplasms

Answer 2

Question 3

Mastocytosis-category chronic myeloid neoplasms

Answer 3

Question 4

Chronic myeliod or lymphoid neoplasms with eosinophilia and gene rearrangements

Answer 4

Question 5

Chronic myeloid neoplasms categorized as MDS/MPN overlap

Answer 5

Question 6

Broad subcategories of chronic myeloid neoplasm characterized by MDS

Answer 6

Question 7

The patient seems to have a CML-like phenotype, but cytogenetics is negative for t(9;22).

What is the next step?

Answer 7

Orthogonal assessment for BCR-ABL1 rearrangement by FISH or RT-PCR

(preferably RT-PCR)

Question 8

Types of BCR-ABL1 fusion protein

Answer 8

p210: Most common, classic disease phenotype, BCR exon 14 conjugated to ABL1 exon 3.

p230: Second most common, more prominent neutrophilic maturation and/or thrombocytosis, produced by BCR exon 12 fusion to ABL1 exon 3.

p190: Least common, but is often associated with more monocytic differentiation, produced by BCR exon 13 conjugated to ABL1 exon 2 or 3.

Question 9

Molecular findings of chronic neutrophilic leukemia

Answer 9

CSF3R mutations

may be accompanied by SETBP or ASXL1 mutations. (only ASXL1 portends a worse prognosis)

Question 10

Molecular findings of primary myelofibrosis

Answer 10

50-60%: JAK2 mutation
30%: CALR mutation
8%: MPL mutation

Question 11

Molecular findings of essential thrombocythemia

Answer 11

50-60%: JAK2 mutation
30%: CALR mutation
3%: MPL mutation

Question 12

Molecular findings of chronic eosinophilic leukemia, NOS

Answer 12

No disease-specific mutation, but demonstration of somatic mutations provides evidence of clonality.

On karyotype, +8, 7-, and Iso17q are common.

Question 13

Mutations in the ‘general myeloid’ category which may be associated with almost any myeloid neoplasm

Answer 13

ASXL1
EZH2
TET2
IDH1
IDH2
SRSF2
SF3B1

Question 14

Summary of the MPN genes

Answer 14

Question 15

Type of JAK2 mutation sometimes found in B-ALL

Answer 15

JAK2 exon 14

Whereas conventional PV is usually JAK2 V617F or less often JAK2 exon 12

Question 16

Most known pathogenic CALR mutations are. . .

Answer 16

delins-type mutations located in exon 9, giving rise to frameshifts that alter the reading frame.

The most common exon 9 alterations are a 52bp deletion (Type 1) and a 5 bp insertion (Type 2)

Question 17

MPL hotspot mutation

Answer 17

MPL W515_

Question 18

Most common KIT hotspot mutation

Answer 18

D816V

Question 19

Prognosis in chronic myeloid/lymphoid neoplasms with eosinophilia

Answer 19

Good for PDGFRA/B, since imatinib and other TKIs work on these proteins.

Not as good for FGFR1 or JAK2 fusions, which have fewer, more inconsistently effective TKIs.

Question 20

Non-TKI fusion partners in chronic myeloid/lymphoid neoplasms with eosinophilia

Answer 20

Very variable - eight partners have been reported for PDGFRA, over 30 for PDGFRB, 14 for FGFR1.

So, it is a good rule of thumb to just be suspicious of ANY potential translocation involving PDGFRA/PDGFRB/FGFR1/JAK2 in these clinical scenarios.

Question 21

Carve-out diagnosis under the umbrella of chronic myeloid/lymphoid neoplasms with eosinophilia

Answer 21

Myeloid/lymphoid neoplasms with JAK2::PCM1 fusion