Page 469 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 23 ■ Myeloproliferative Neoplasms 453

Initial Phase

T e onset o the e rly, initi l ph se (chronic ph se) o CML

is insi ious n y l st ro 3 to 5 ye rs. Most c ses (85%)

re i gnose in this ph se. Signs n sy pto s c n inclu e

progressive tigue n l ise, low-gr e ever, norexi ,

weight loss, n bone p in. Night swe ts n ever, ssoci te

with n incre se et bolis c use by gr nulocytic cell

turnover, y occur. Physic l ex in tion usu lly reve ls

splenic enl rge ent. Splenic in rction is co on bec use

o the bnor l overpro uction n ccu ul tion o gr n-

ulocyte precursors in the bone rrow, spleen, n bloo .

T ese in rcts in the spleen y pro uce le upper qu r nt

p in. Any org n y eventu lly be inf ltr te with yeloi

ele ents. Extr yeloi sses in re s other th n the spleen

n liver, however, re unco on f n ings in the chronic

ph se. On resh incision, extr yeloi sses ppe r green,

presu bly bec use o the presence o the yeloi enzy e

yeloperoxi se. T ese greenish tu ors h ve been c lle

FIGURE 23.3 Oncogene ctiv tion by chro oso l tr nsloc tion. chloromas.

A: Chronic yelogenous leuke i . Bre ks t the en s o the long

r s o chro oso es 9 n 22 llow reciproc l tr nsloc tions to Accelerated Phase

occur. T e c- bl protooncogene on chro oso e 9 is tr nsloc te A tr nsition l, cceler te perio y prece e bl st tr ns-
to the bre kpoint region (BCR) o chro oso e 22. T e result is or tion. T is tr nsition is her l e by n incre se in

the Phil elphi chro oso e, which cont ins new usion gene splenomegaly, rising peripher l bloo leukocyte count, n

co ing or hybri oncogenic protein, presu bly involve in the

p thogenesis o chronic yelogenous leuke i . B: Burkitt ly - incre se percent ge o b sophils, worsening ne i , n
pho . In this isor er, chro oso l bre ks involve the long r s thro bocytopeni .

o chro oso es 8 n 14. T e c- yc gene on chro oso e 8 is

tr nsloc te to region on chro oso e 14 j cent to the gene Blast Crisis (Acute)

co ing or the const nt region o n i unoglobulin he vy ch in In the p st, CML virtu lly lw ys progresse to bl st crisis.
(C ). T e expression o c- yc is enh nce by its ssoci tion with re t ent to y slows own bl st crisis in ost p tients n
H
the pro oter/enh ncer regions o the ctively tr nscribe i u- possibly presents it in so e. T e ost recent WHO ef ni-

noglobulin genes. (Reprinte ro Rubin E, F rber JL. Pathology, tion proposes bl st count o 20% in n logy to the ef ni-

3r e , Phil elphi , PA: Lippincott Willi s & Wilkins, 1999, with tion o cute yelogenous leuke i . P tients with 20% to
per ission.) 29% bl sts, currently cl ssif e s cceler te ph se, h

signif c ntly better prognosis th n p tients with ore th n

roles in sign l tr ns uction n the regul tion o cell growth. 30% bl sts.

V rious structur l lter tions o ABL n BCR genes cili- About three ourths o p tients eventu lly enter gr -

t te the leuke ogenic tr ns or tion. u l tr ns or tion to bl st crisis. T e bl st crisis ph se

is ch r cterize by the ppe r nce o pri itive bl st cells

Clinical Signs and Symptoms si il r to those seen in cute leuke i . T e bl st ph se is

ef ne by the presence o 30% or ore leuke ic cells in
T e clinic l course o CML c n be ch r cterize by three peripher l bloo or rrow or the presence o extr e -

sep r te progressive ph ses ( ble 23.2).
ull ry inf ltr tes o bl st cells. Acute-ph se CML is he -

tologic lly n clinic lly in istinguish ble ro cute

Typical Phases of Chronic leuke i . In one thir o c ses, the bl sts h ve ly phoi
TABLE 23.2
Myelogenous Leukemia orphology n express ly phoi rkers such s ter i-
n l eoxynucleoti yl tr ns er se ( ) or CD10 (co on

Approximate cute ly phobl stic leuke i ntigen). T e re ining two

Length of thir s o c ses h ve phenotype si il r to th t o cute

Phase Phase Treatment Status* yelobl stic leuke i n or heterogeneous group.

M king istinction between the two is i port nt bec use
Initial (chronic) 2–5 y Highly treatable
p tients whose leuke i is in the ly phoi bl st ph se

Accelerated 6–18 mo Resistance develops respon to tre t ent with regi ens th t re ctive g inst

Blast crisis (acute) 3–4 mo Generally cute ly phoi leuke i .
unresponsive Excessive blee ing or bruising s well s evers y

be ni este in the l ter st ge o CML. Co plic tions
*Treated with chemotherapy.
re requent in conjunction with the bl st crisis. Blee ing