Page 475 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 23 ■ Myeloproliferative Neoplasms 459

Chronic Eosinophilic Leukemias o white bloo cells, such s neutrophils or st cells.

Occ sion lly, p tients with PDGFRA- ssoci te chronic
A ong the hypereosinophilic syn ro es (HESs), there is eosinophilic leuke i evelop other lign ncies such s

continuu o hypereosinophilic ise se. At one o the cute yeloi leuke i or B- or -cell cute ly phobl stic

spectru is the eosinophilic MPN, eosinophilic leuke- leuke i or ly phobl stic ly pho .

i . At the other en o the spectru re benign con i-

tions such s p r sitic in ection, sth , llergies, or rug Chronic Eosinophilic Leukemia, Not

hypersensitivity. Otherw ise Speci ed (CEL-NOS)

PDGFRA-Associated Chronic Eosinophilic T is clon l MPN presents with eosinophili not cl ssi-

Leukemia f e s nother neopl stic con itions. T is con ition l cks

PDGFRA, PGDFRB, n FGFR1 ut tions.
PDGFRA- ssoci te chronic eosinophilic leuke i is r re CEL-NOS is ef ne by the ollowing criteri :

con ition. T e ex ct inci ence is unknown. M les re ore

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likely to evelop this or o leuke i th n e les. ■ ot l peripher l bloo eosinophil count o ≥1.5 × 10 /L
T e bone rrow is hypercellul r bec use o eosinophilic th t persists over ti e

proli er tion n c n exhibit Ch rcot-Ley en cryst ls. Bone ■ Evi ence o clon lity or gre ter th n 2% yelobl sts in

rrow f brosis exists ue to the rele se o eosinophilic b sic peripher l bloo n 5% to 19% yelobl sts in the bone

protein n eosinophilic c tionic proteins ro the eosino- rrow

phil gr nules. ■ ot l peripher l bloo leukocyte count gre ter th n 30 ×

9
T e presence o yelobl sts is less th n the 20% threshol 10 /L with 30% to 70% eosinophils
th t is necess ry to cl ssi y the con ition s cute leuke i . CEL-NOS is excluded by the presence o :

Erythrocytes n eg k ryocytes re nor l in nu ber but

y e onstr te yspl stic orphology. ■ All secon ry c uses o eosinophili

New olecul r n i unologic ss ys h ve en ble ■ Neopl stic isor ers with secon ry eosinophili

ore ef nitive etiologic cl ssif c tions, especi lly those c ses ■ Aberr nt phenotypic -cell popul tion

ssoci te with eosinophilic MPNs. PDGFRA- ssoci te ■ Neopl stic isor ers when eosinophils re p rt o the neo-

chronic eosinophilic leuke i is c use by ut tions in the pl stic clone such s cute yelogenous leuke i

PDGFRA gene. As result o this ut tion, n bnor l ■ PDGFRA, PDGFRB, or FGFR1 ut tions

protein known s FIP1-like 1/pl telet- erive growth ctor ■ Chro oso l bnor lities: inv(16)(p13. 1q22) or

lph is synthesize . t(16, 16)(p13.1:q22) or other i gnostic e tures o cute

A ch r cteristic e ture o PDGFRA- ssoci te chronic yelogenous leuke i

eosinophilic leuke i is org n ge c use by the excess ■ BCR-ABL1 usion gene

eosinophils. Bone rrow f brosis contributes to the pre-

ture rele se o eosinophils into the peripher l circul tion

n subsequently eposite in v rious tissues. Eosinophils NOTE: This is a good time to complete Review Questions

rele se subst nces to i in the i une response, but the related to the preceding content.

rele se o excessive ounts o these subst nces c uses

ge to one or ore org ns, ost co only the he rt,

skin, lungs, or nervous syste . Eosinophil- ssoci te org n POLYCYTHEMIA VERA, ESSENTIAL

ge c n le to he rt con ition known s eosinophilic THROMBOCYTOSIS (ESSENTIAL

en o yoc r i l ise se. THROMBOCYTHEMIA), AND PRIMARY

T e in criteri or i gnosing PDGFRA- ssoci te MYELOFIBROSIS

chronic eosinophilic leuke i re:

Polycythemia rubra vera PRV , essenti l thro bocytosis
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■ A tot l peripher l bloo eosinophil count o ≥1.5 × 10 /L or essential thrombocythemia (E ), n PMF were i enti-
th t persists over ti e fe s p thogenetic lly rel te yeloproli er tive isor ers

■ Bone rrow hypercellul rity n f brosis in 1951.

■ No p r sitic in ection, llergic re ction, or other c uses o Subsequently, PRV, E , n PM were i entif e s clon l

eosinophili isor ers o ultipotent he topoietic progenitors. In 2005,

■ Elev te bloo levels o vit in B n trypt se so tic ctiv ting ut tion in J nus kin se (JAK2) nonre-
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■ Spleno eg ly
ceptor K (JAK2V617F) w s i entif e in ost p tients with

P tients with PDGFRA- ssoci te chronic eosinophilic leu- PRV n in signif c nt proportion o p tients with E n

ke i re exquisitely sensitive to i tinib esyl te n shoul PM ( ble 23.5).

receive it s f rst-line ther py. He tologic re ission occurs Subsequently, ition l ut tions in JAK-S A p th-

within ys n olecul r re ission is l ost univers l. w y in so e p tients with JAK2V617F-MPN suggeste th t

So e p tients with PDGFRA- ssoci te chronic eosino- constitutive ctiv tion o this sign ling p thw y is uni y-

philic leuke i h ve n incre se nu ber o other types ing e ture o these isor ers. JAK2 is nonreceptor protein